Is the Twelve Core Random Biopsy for Prostate Cancer Obsolete?

A perfect test for prostate cancer should detect high-grade prostate cancer accurately while avoiding the over-diagnosis of harmless, low-grade cancers (the Gleason 6 variety). Back in 2011, the US Preventative Services Task Force (USPSTF) recommended against further PSA testing in healthy men because of the rampant over treatment of low-grade cancers. The problem was so out of hand, the only solution they could come up with was to discourage PSA screening.

However, over the last five years since these initial recommendations were made, it has become apparent that the real cause of over-diagnosis is the random 12-core needle biopsy, not PSA.

Unfortunately, a 12-core random biopsy continues to be the standard approach in men with elevated PSA. However, recently-developed technology offers an alternative to doing a random biopsy. It turns out that imaging with multi-parametric MRI (mp-MRI) is an excellent substitute for random biopsy. The great thing about mp-MRI is that it accurately detects high-grade prostate cancer without over diagnosing the harmless type of prostate cancer (Grade 6). A number of new studies pertinent to this topic were presented at the 2016 American Urology Association (AUA) meeting in San Diego. This article reviews these important studies, suggesting that prostate imaging at centers of excellence using 3T multi-parametric MRI accurately identifies high grade cancer and has advantages over random biopsy.

The Studies Behind Prostate Cancer Diagnosis Tests

Since the main problem with PSA screening is that it almost always leads directly to a 12-core random biopsy, the first study I would like to present relates to the potential dangers of random biopsy.

Abstract MP53-13 authored by Dr. Alaina Garbens, looked at how often men were hospitalized after a random biopsy.

She looked at hospital admission rates of 61,910 men who underwent random biopsy in Ontario, Canada between January 2006 and December 2013. This study evaluated mortality rates and hospital admission rates within the first 30 days after a prostate biopsy was performed.

They found that the chance of dying from a biopsy was one in ten-thousand. The rate of hospital admission within the first 30 days after the biopsy was 3.5 percent. Of that 3.5 percent, three-fourths of the men were admitted for the treatment of an infection. As a side note of this study, Dr. Garbens also noted that the number of biopsies being performed dropped 30.6 percent compared to the number of biopsies performed prior to the USPSTF recommendations.

Two addition studies presented at the AUA looked further into how the USPSTF recommendations are affecting the type of cancer being diagnosed. Both of these studies show a sizable increase in the grade of cancer being diagnosed since the USPSTF made its recommendation to forgo screening.

Abstract MP39-04 by Dr. Carl Olsson reported that the USPSTF recommendations in 2011 were published recommending that doctors forgo PSA screening—more men being diagnosed with higher grade cancers:

Year

Men Gleason 8 to 10

2010

2011

14.8%

14.8%

2013

19.7%

2014

25.4%

Clearly, the percentage of men being diagnosed with high-grade prostate cancer is steadily increasing. 

Abstract PD09-03 authored by Dr. Glen Gejerman also compared the grade distribution of new cases diagnosed before and after the USPSTF recommendations. He evaluated 2513 men who were biopsied in 2011 and 1665 who were biopsied in 2014. The median Gleason score changed from 6 in 2011 to 7 in 2014. High Gleason scores (8-10) were diagnosed in 19 percent of the 2014 biopsies versus only 9 percent of the biopsies performed back in 2011.

The preceding studies indicate that the USPSTF recommendations to forgo PSA screening are reducing the number of men undergoing PSA screening. The net effect is a reduction in diagnosis of Gleason 6—a low grade form of prostate cancer of men who undergo a biopsy. This was the intended effect of the USPSTF recommendations. When the USPSTF made their recommendations back in 2011, there was no alternative to doing a 12-core random biopsy for evaluating men with high PSA levels. So to cut back on the serious problem of over-diagnosing low grade disease, the USPSTF made the decision to discourage PSA screening altogether.

What this means: This recommendation might have made sense back in 2011. However, now there is new technology that provides a viable alternative to doing a random biopsy.

The next six studies listed from the 2016 urology meeting show that multi-parametric MRI followed by a targeted biopsy accurately detects high-grade prostate cancer and greatly curtains the problem of over-diagnosing grade 6.

Abstract MP16-17 authored by Dr. Yasukaza Nakanishi evaluated the accuracy of doing a targeted biopsy of suspicious lesions detected with a 3T multi-parametric MRI (mp-MRI) of the prostate. He compared the results of doing a targeted biopsy with the results obtained by doing a 14-core random biopsy. In his study, he evaluated 202 men with high PSA levels with a multi-parametric MRI (mp-MRI). All suspicious lesions detected by mp-MRI (PI-RADS-3 an above) were targeted. “High-grade” cancer was defined as Gleason score ≥4+3 or maximum cancer length ≥5 mm. They found that a targeted biopsy detected 88 percent of the men who had significant cancer and 97 percent of men who had disease that was Gleason 8 or higher.

Abstract PD15-08 authored by Drs. Peter Choyke and Peter Pinto evaluated the underlying causes for high-grade disease being missed by targeted biopsy in 1003 men. They reported that a targeted biopsy missed Gleason 7 disease in 11 percent of men and missed Gleason 8 or higher in 2 percent. Re-review of the mp-MRI images of these patient showed that two-thirds of them had a visible lesion that was missed by the doctor interpreting the scan. In almost all of the remainder, the doctor doing the needle biopsy simply missed the lesion. Only 1 percent of the men had a truly MRI-invisible cancer. In other words, in most cases the failure of targeted biopsy to find cancer was due to suboptimal reading of the MRI or suboptimal targeting by the doctor doing the needle biopsy. Apparently, the imaging is working fine, but a patient needs to be aware that it won’t be reliable unless it is skillfully implemented by trained and experienced doctors.

Abstract PD15-11 authored by Dr. Amanda Lu evaluated the negative predictive value of mp-MRI compared to random biopsy. “Negative predictive value” means the likelihood missing cancer when it is present. Men with elevated PSA whose mp-MRI showed no aggressive lesions underwent a 12-core random biopsy. Out of 53 men with a mp-MRI showing no lesion, only 3.8 percent were found to be harboring cancer that was clinically significant cancer (Gleason≥7) as determined by the 12-core biopsy.

Abstract MP21-15 authored by Dr. Jan Philipp Radtke compared the detection accuracy of mp-MRI with surgery. He evaluated 120 men who underwent mp-MRI directed fusion biopsy prior to surgery. The mp-MRI detected 110 (92 percent) of the significant lesions compared to the pathologic findings after surgery. Of these, fusion biopsy diagnosed 80 percent of these high grade lesions. Again, this illustrates the need to have skillful and experienced doctors to do the targeted biopsy.

Abstract MP53-02 authored by Dr. Joseph Mahon reviewed the records of 395 men with an elevated PSA for the presence of underlying prostate cancer. All the men had undergone a mp-MRI prior to random biopsy. Men without any significant lesions detected on the mp-MRI or with low-grade lesions thought not to be cancer (PI-RADS 1-2) were evaluated. One hundred and sixty nine men fulfilled these criteria and were included in the study. They all underwent a random 12-core biopsy.  Overall, prostate cancer was noted in 54 (32 percent) men of which 47 (88 percent) were Gleason 6 or uni-focal Gleason 3+4. Significant disease, i.e., Gleason 4+3 was diagnosed in 10 percent of the men and Gleason 4+4 was noted in 2 percent. In other words, the negative predictive value of a normal mp-MRI in this particular study was 88 percent.

Abstract MP53-15 authored by Drs. Peter Choyke and Peter Pinto evaluated the accuracy of mp-MRI fusion biopsy in a multi-institutional review. The men in the study underwent an initial mp-MRI followed by fusion biopsy which was then followed by a 12-core random biopsy. The type of prostate cancer diagnosed was subdivided into three categories: Low-risk (Gleason 6 or low volume Gleason 3+4=7), Intermediate-Risk (high volume Gleason 3+4=7), and High-Risk (Gleason of 4+3 or higher).

A total of 395 biopsy-naive men were identified from 4 participating institutions. Fusion biopsy diagnosed more High-Risk disease than 12-core biopsy (22.3 percent vs 20.3 percent). Additionally, fusion biopsy detected 18 percent fewer cases of Gleason 6 (15.7 percent vs 19.2 percent). Fusion biopsy only missed four men with Intermediate-Risk and one with High-Risk that were diagnosed by random biopsy.

What this means: The preceding six studies show that mp-MRI directed fusion biopsy diagnoses high-grade disease at least as well as random biopsy, if not better. But the real advantage of mp-MRI over random biopsy is the lower detection rate for low-grade cancer. The other beauty of mp-MRI is some men can forgo biopsy altogether. In the men who require a biopsy, far fewer biopsy cores are needed.

The final study from the AUA meeting that is pertinent to this topic addresses the question of cost.

Abstract MP53-14 authored by Drs. Peter Choyke and Peter Pinto from the National Cancer Institute in Bethesda,  explored the cost-effectiveness of prostate MRI compared to random biopsy. The cost for 100 men undergoing random biopsy of ($1,410 per man) is $141,035. Random biopsy would be falsely negative in 13 men and falsely positive 24 men. 

The cost of a mp-MRI of $633 and MRI fusion biopsy of $2,138.  The total cost of obtaining initial prostate MRI in 100 men with only patients with target lesion(s) undergoing a targeted biopsy, was determined to be $107,961.69 given that 70 men would undergo prostate MRI alone, and 30 men would have a subsequent targeted biopsy. Within the group of men only undergoing prostate MRI, 7 men would have falsely negative results and 9 would have falsely positive results. Overall fusion biopsy would cost 25 percent less than undergoing a random biopsy.

What this means: Information about prostate imaging from the annual urology meeting indicates that 3T multi-parametric MRI accurately identifies high grade cancer. The advantages over random biopsy are many: A lower incidence of being diagnosed with Grade 6, lower cost, fewer men who require biopsy and fewer complications from biopsy. The only caveat to keep in mind is that a properly performed mp-MRI requires state-of-the-art equipment and experienced, well-trained doctors who read the scans.  Therefore, until this technology becomes more widespread, you may need to travel to another city to ensure you are getting your scan done in a center of excellence.

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