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. 

PSA Screening for Prostate Cancer

BY MARK SCHOLZ, MD

Most elderly men already have prostate cancer—they just don’t know they have it.  And they might be better off remaining ignorant. Newly-diagnosed men are thrown into an eight-billion-per-year medical world that extols radical treatment. Over-treatment is so out-of-control that a New England Journal of Medicine study estimates that forty-eight men are getting unnecessary surgery or radiation for each individual who truly benefits from them.

Random Biopsy, Not PSA is the Real Problem
When PSA is elevated, primary care physicians usually refer to a urologist for an immediate 12-core random prostate biopsy. One million men are biopsied annually in the United States. Few people realize that even when the PSA is normal, the biopsy will be positive 20% of the time. The problem is that a diagnosis of any prostate cancer, even the Low-Risk type, almost invariably leads to surgery or radiation.

Biopsies Are Not Benign
Over-diagnosing Low-Risk prostate cancer, and the attendant risk of over-treatment, is not the only problem caused by random biopsy. Consider the emotional devastation caused by a cancer diagnosis. Men are literally frightened to death by the discovery of prostate cancer: The first week after diagnosis, the risk of suicide and heart attacks jumps dramatically. In addition, 3% of men suffer biopsy-induced infections resulting in hospitalization. Fatal infections are estimated to occur in approximately one-thousand men undergoing random biopsy per year.

Stop PSA Screening?
Due to all these mounting negatives, the US Preventative Services Task Force now recommends that routine PSA testing cease altogether. The Task Force’s conclusion was that unnecessary treatment to over a hundred thousand men annually is too big a price to pay even though PSA screening saves lives. The Task Force fails to understand that overtreatment isn’t caused by PSA, it’s what physicians do with the information PSA provides—they automatically refer every patient for immediate random biopsy.

PSA Is Heavily Influenced by Prostate Size
Most PSA originates from the prostate gland, not from cancer. Therefore, when the cancer is relatively small, PSA is a reflection prostate gland size. In a man without cancer, PSA normally averages one-tenth of the prostate volume. For example, the average PSA for a 30cc prostate is 3; five for a 50cc prostate and 10 for a 100cc prostate with size determined by ultrasound or MRI.

Therefore, PSA can only be termed “abnormal” if it’s 50% higher than expected, based on a man’s prostate size. For example, an abnormal PSA for a 30cc prostate is 4.5, a 50cc prostate, 7.5 and a 100cc prostate, 15. Additional extraneous factors such as low-grade infections, lab variations and recent sexual activity can also cause PSA to vary.  Repeat testing helps average out these variations so the “real” PSA can be determined.

Primary Care Doctors Are the Source for Balanced Counsel
Only the primary care physicians can stop the mindless rush to random biopsy. Instead of referring for random biopsy they can send their patients with elevated PSA for prostate imaging with multiparametric MRI or Color Doppler Ultrasound. Imaging can put the PSA elevation into context by determining the prostate size. Also, in the hands of an experienced radiologist, using state-of-the-art, three-Tesla MRI, high-grade cancer can be ruled out with 95 to 98% accuracy.

If imaging detects a high-grade lesion, primary physicians can then counsel their patients about whether a targeted biopsy directed at the abnormal lesion should be performed. Alternatively they can recommend simple monitoring with a repeat imaging study six to twelve months down the road to determine if the lesion is growing. Lastly, if a targeted biopsy shows cancer, rather than being guided by a urologist, who is, after all, a surgeon, patients can obtain counsel from their primary physician, a non-surgeon who can provide unbiased assistance in selecting the best treatment.

Estimating Cancer Risk
If men are concerned about the risk of forgoing an immediate random biopsy they can estimate the percentage likelihood of harboring low-grade or high-grade disease with an online calculator by googling, “risk of biopsy-detectable prostate cancer.”

Imaging Rather than Biopsy
Prior to PSA screening men should be informed that if PSA is high, the first step should be imaging rather than random biopsy. Random biopsy can cause serious infections. It also diagnoses Low-Risk prostate cancer, a harmless condition that nevertheless, often leads to unnecessary treatment. PSA screening, while saving lives by detecting High-Risk cancer at an early stage, can also, if handled improperly, lead to unnecessary treatment with many lifelong side effects.   

Dying for a Biopsy?

MARK SCHOLZ, MD

Screening for prostate cancer is big business. The PSA blood test, first implemented in the late 1980s, resulted in a doubling in the number of new cases, from 100,000 a year to more than 200,000 annually. The cost of simply diagnosing prostate cancer—after adding up doctor, lab and pathology charges—easily surpasses a billion dollars annually.

Cancer is diagnosed by a specially-trained doctor, a pathologist, who examines the prostate tissue under a microscope. Tissue is extracted by needle biopsy, a procedure that is performed in a doctor’s office. The patient lies on his side and an ultrasound probe is inserted into the rectum. Then after Novocain is injected, 12 to 14 tissue samples are removed using a spring-loaded needle gun that is fired in a grid pattern over the surface of the prostate . The tissue samples are then transported to the pathologist who determines whether or not cancer is present.

Over a million men undergo a prostate biopsy each year. Immediate biopsy at the first sign of PSA elevation has been the standard approach for more than 30 years. However, this policy needs to be reconsidered. Last year the US Preventative Services Task Force reconfirmed their strong warning against PSA screening, pointing out that it leads directly to an egregious degree of overtreatment in men with microscopic amounts of harmless low-grade prostate cancer.  The problem is that surgery and radiation induce shockingly high rates of permanent sexual dysfunction and loss of urinary control. These are distressingly serious problems when considering that treatment is frequently unnecessary in the first place.

Until recently, the needle biopsy procedure itself was perceived as being reasonably safe. However, two just-released studies indicate that it is nowhere near as innocuous as most physicians had assumed.  For example, at the American Urology Association meeting in May, doctors from Memorial Sloan Kettering reported that infectious complications requiring hospitalization occur 2.8% of the time.* In a separate study at the American Society of Clinical Oncology meeting, Dr. Boniol from the International Prevention Research Institute reported that 1.3 deaths occurred for every 1,000 men who undergo biopsy. To put this latter finding in perspective, Dr. Boniol commented, “This prostatic biopsy mortality would occur earlier than any benefit from a screening program and could reverse any potential gain from screening…”

Fortunately, there is an alternative to immediate biopsy.  MRI scanners can guide a biopsy needle directly to the area of the prostate gland where the disease is located, thus allowing a reduction in the number needle biopsies by 90%.  While there are drawbacks to this new technology—it requires special training and the equipment is expensive—the risk of serious infections should be much lower.

Change is often resisted by the status quo, especially when it involves a major shift in reimbursement patterns.  Doctors who do random prostate needle biopsies will likely view these technological advancements with suspicion. Even so, the 30-year old methodology of puncturing the prostate with multiple random needle sticks is overdue for replacement. Noninvasive MRI imaging technology to detect prostate cancer is a far more sensible way to evaluate men with rising PSA levels. 

*Abstract 1244 -The Impact of Repeat Biopsies on Infectious Complications in Men with Prostate Cancer on Active Surveillance: a Prospective Study