The co-authors of Invasion of the Prostate Snatchers, blog alternate posts weekly. We invite you to post your comments.

Tuesday, December 17, 2013

PSA Screening for Prostate Cancer


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.   

1 comment:

Anonymous said...

I wholeheartedly agree with what you write regarding the reliance on multiparametric MRI to rule out high-grade cancer. The decision to submit to a biopsy is rather easy when the MRI results are presented with a stated confidence level greater than 95%.

However changes visible in the MRI from advanced cancers are significantly greater and presumably easier to spot than those for less advanced disease. In the latter, malignant cells are less abnormal and therefore harder to discern. Moreover, often the volume of concern is smaller in size. What does one do if the expert radiologist says, based on a multiparametric MRI analysis, that he suspects there is an intermediate-grade cancer, but that he is only 60% confident of this MRI-based diagnosis?

That more or less was the news I recently received recently at a prestigious urology clinic that graciously altered their usual routine for me because of my wariness of undergoing a biopsy despite my doctors finding a palpable nodule in my DRE. (At this point I had not even read The Prostate Snatchers.) As a chemist and former spectroscopist as well as a patient, I am in the somewhat unusual position of being sufficiently familiar with magnetic resonance spectroscopy to appreciate the years of research and complexity of interpretation that had to be developed to make such a reliable assessment as even 60% confidence. Therefore I asked whether addition of one tool they were not using might significantly improve the specificity of their assessment, namely MRI spectroscopy to examine choline, citrate, or other chemical fingerprints of malignancy. I was told that MRI-S is not quite developed to the point that it is highly reliable for clinical use, and of course I surmise it might be considerably more expensive (even though my clinic is billing $8,300 for the "ordinary" multiparametric MRI), as well as less available and likely nonreimbursable on most insurance plans. I have seen the studies suggesting otherwise regarding the utility of MRI-S (for example, see Invest Radiol 2011;46: 25–33, describing results of an 8-center trial), but I know there is a barrier to translating research into the clinical world.

I also wonder whether or not these enhancements in MRI have developed to the point where they can actually give sufficiently definite interpretations to remove from diagnostic limbo a case such as mine. Unlike my DRE and radiologist's MRI report, my laboratory data are relatively favorable: PSA=3.5, free PSA=27%, PSA density=0.12, and PSA velocity=0.25 (but over a 7-year interval, because I had abandoned regular PSA testing as advised by many experts in 2007). It is my understanding that even my PCA3, while high enough at 33 to be suspicious, is very low for anything but a low-risk cancer, unless perhaps it has been caught very early.)

A recent assessment by your colleague, John Kurhanewicz, whom my research has confirmed to be a leading expert in the field of MRSI, is included in chapter 23 of Prostate Cancer Diagnosis: PSA, Biopsy and Beyond, in the Current Clinical Urology series, Humana Press, J.Stephen Jones, Ed., 2013, For the combo of proton MRSI and DCE MRI in a prior negative biopsy population, he cites a reference reporting sensitivity, specificity and accuracy numbers exceeding 90%.

Given my current predicament, far from unique, I wonder if you could comment in general on the utility of imaging in these less than clearcut cases. Assuming the suspected lesion is large enough relative to the limited spatial resolution of MRI-S, has the latter advanced to the point that it can really take the place of a biopsy in grading intermediate-risk prostate cancer with a degree of confidence approaching that of a needle biopsy--when multiparametric MRI without MRI-S is unable to do so? (Note also Jose's comment on your 2013/07/dying-for-biopsy.html blog, regarding equivocal findings from 3.0 T MRI-S on his two relatively small lesions of 8 and 5 mm.)