Alternatives to Immediate Prostate Biopsy

BY MARK SCHOLZ, MD

Your PSA is elevated. Now your doctor recommends a needle biopsy, 12 cores through the rectum to check for cancer in the prostate.  Sounds icky, but also logical; after all who wants to miss cancer? But come on, do you really have to do 12 stabs via the rectum?

Each year over a million men submit their prostates for a biopsy.  At an average cost of around four thousand dollars, the prostate biopsy business is a 4-billion-dollar-a-year enterprise.  But it’s not merely the cost that gives pause.  Three percent of men end up hospitalized with life-threatening infections.  Around a 100,000 men every year get a confounding diagnosis of Grade 6 prostate cancer, a truly harmless entity, unless you get suckered into an unnecessary radical prostatectomy.

Obviously, prostate biopsy is an unpleasant proposition with notable risks.  However, ignoring a high PSA incurs the risk of missing a diagnosis of a higher grade prostate cancer. As things stand now, of the million biopsies being done annually, over a hundred thousand men with Grade 7 or higher cancers are being detected. For these men, their early diagnosis is beneficial, leading to early, curative treatment in a timely fashion.

How can we detect the 100,000 men with higher-grade cancers that need to be detected without doing 900,000 “unnecessary” biopsies?   The answer to this question continues to evolve as technology marches forward. Our latest thinking at Prostate Oncology (assuming the PSA is not wildly elevated, say over 20) is a three step process:

1.    Simply repeat the PSA to confirm it is indeed abnormally elevated.  All sorts of things can cause temporary elevations of PSA ranging from nonspecific inflammation of the prostate, to recent sexual activity, to simple laboratory errors. 

2.    If the PSA remains elevated with repeat testing the next step to consider is an OPKO-4Kscore blood test. The OPKO test reports a percentage estimate of the likelihood of higher grade cancer being present.  The test is not perfect, but it performs pretty well.  For example, if a specific patient receives an OPKO report with an estimated risk of high grade disease of less than 15%, a standard random biopsy (if he elected to do one) will confirm the absence of high grade disease 92% of the time. Not bad.

3.    Our next step at Prostate Oncology, in the cases where a patient has an OPKO test indicating that the risk of high grade disease is over 15%, is to obtain a prostate scan with high-resolution color Doppler ultrasound or with a 3-Tesla multiparametric MRI. With scanning, the location of the high-grade disease can be determined over 90% of the time so that a targeted biopsy with 2 or 3 cores can be substituted for the traditional 12-core biopsy.       

The business of prostate biopsy has become so out of control the US Preventative Services Task Force advocates against PSA testing altogether.  The Task Force’s scientifically-based arguments that PSA testing is causing more harm than good are really quite convincing.  However, back in 2011 when they published their recommendations, the OPKO test and 3-Tesla multiparametric prostate MRI were unavailable. With the advent of these new technologies, PSA screening to detect higher grade prostate cancers at an early stage when they are still curable makes perfect sense. 

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.

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. 

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.”

A Prostate Biopsy Can be Dangerous

BY MARK SCHOLZ, MD

Last August, I railed against too many biopsies. However, my experience at a recent prostate cancer meeting prompted me to revisit the topic for today’s blog.  There is now general agreement among experts that prostate cancer is over-diagnosed.  I believe this results from the excessive use of random prostate biopsy and, all too often, leads to radical over-treatment.

More than a million men in the United States have prostate tissue extracted by transrectal needle biopsy every year. Of all those biopsied, one-fourth, about 240,000 men, are diagnosed with prostate cancer. Of these 240,000, between one-third and one-half—that is, from 80,000 to 120,000—are diagnosed with a harmless condition destined to remain dormant for life. And yet, despite the innocuous nature of low-grade prostate cancer, the great majority of these unfortunate men still undergo radical treatment with decidedly negative impact on their quality of life.

The unwillingness of surgeons and radiation therapists to withhold treatment for low-grade prostate cancer is not entirely surprising given that doctors are specifically trained to treat cancer.  Understandably, patient enthusiasm for treatment is also a major contributing factor, considering how dangerous it would be to withhold treatment of most any other type of cancer.

The overtreatment of prostate cancer is giving experts sufficient concern that editorials are appearing in prestigious scientific journals, such at the Journal of Clinical Oncology and Lancet Oncology, discussing the possibility of renaming low-grade prostate cancer something besides “cancer.” Everyone seems to agree that it’s unreasonable to name a condition cancer when we know this low-grade form doesn’t usually metastasize.

Given these daunting issues, I was interested to survey a group of twenty male experts at a prostate cancer meeting last month about their attitudes toward biopsy.  Because the average age of the group was around sixty, everyone in the group readily agreed that if all of us underwent a standard random biopsy at least five would be diagnosed with prostate cancer. With such a high statistical risk of finding cancer, I then asked by a show of hands if anyone was interested in having a biopsy.

While an unnecessary cancer diagnosis is one risk of biopsy, there is one other significant risk: the possibility of toxic effects of biopsy itself.  The Journal of Urology this month reports that with prostate biopsy the rate of infections serious enough to require hospitalization has quadrupled to approximately one in fifty. One out every twenty of these infected men admitted to the hospital actually dies—making the risk of death from biopsy is one in a thousand.

Not a single doctor raised his hand.

Fortunately there is an excellent alternative to random biopsy.  Modern prostate imaging with 3-Tesla MRI or color Doppler ultrasound, is just as accurate for detecting high-grade disease. When an abnormality is detected through imaging, it can be targeted with just one or two biopsy cores instead of randomly shooting a dozen cores throughout the gland. And yet, despite the obvious advantages of imaging and targeted biopsy, practically all biopsies done in the United States are being performed randomly. 

Sadly, the general public—including most primary care physicians and even perhaps the majority of urologists and radiation oncologists—remains uninformed about the advantages of modern imaging technology. For more information about biopsy and Imaging Technology see my March 27, 2012 blog, Biopsy, Biopsy Everywhere: http://prostatesnatchers.blogspot.com/2012/03/biopsy-biopsy-everywhere.html