When the evidence says no but doctors continue to say yes
Screening for prostate cancer is promoted heavily and, at face value seems to be very reasonable. However, what is the objective evidence that the very controversial PSA (prostatic specific antigen) blood test can lead to the early detection and possible cure of significant numbers of men who have only the potentially deadly forms of prostate cancer?
This question is especially important since the all-inclusive prostate cancer label leaves one with the impression that every prostate cancer is potentially lethal. However, in sharp contrast to this misconception the generic prostate cancer label is very deceptive because it includes both pseudo-cancers and, potentially lethal cancers. In fact, only some of the 15 percent or so of high-grade prostate cancers are potentially deadly. A source of confusion that has allowed misguided urologists to game the cancer tag and, use falsehoods and scare-tactics to bully the vulnerable and medically illiterate into unneeded testing and treatments for profiteering. An easy process since the only thing heard by these patients is the terrorizing cancer word.
Which prostate “cancers” fail to behave as cancerous?
Undeniably, for many years the Gleason 6 prostate “cancer” has been misrepresented as a cancer. Although appearing mildly cancerous under the microscope, on both clinical and molecular biology grounds, the Gleason grade 3, as in the Gleason 3+3=6 “cancer” (Gleason 6 or, G6) LACKS the hallmarks of a cancer (L. Klotz MD). Highlighting the non-cancerous behavior of the G6 even more is the fact that the G6 cell has a very long doubling time of 475 +/- 56 days so that from mutation to a growth of about 1 cm (smaller than half an inch) in diameter takes some 40 years. Furthermore, about 50 percent of 50 year-old-men have unrecognized and asymptomatic areas of G6 disease in their prostate and, since there is no objective evidence that this so-called cancer can turn aggressive to harm men, it’s believed that the G6 is simply a part of the aging process. Because of these findings, there is simply NO justification for continuing to call the Gleason 6 a cancer, attempt to detect or, even treat it. In fact, restricting the cancer label to just the potentially lethal high-grade prostate cancers should protect the public from a vast amount of unnecessary and risky “treatments”.
Which prostate cancers are potentially deadly?
Only the 15 percent or so of high-grade/high-risk prostate cancers with significant amounts of pattern (grade) 4 and or 5 disease in their Gleason score require detection and treatment as only these types of prostate cancers are potentially deadly. Furthermore, although prostate cancer kills about 30,000 men annually in the US (second most common cancer cause after lung cancer), only the high-grade prostate cancers are responsible for these deaths.
Aside from these important high-risk prostate cancers there are some that have a mix of grade 3s and 4s in their Gleason score and are grouped into the confusing so-called intermediate-risk category. This intermediate-risk Gleason 7 category actually includes two very differently behaving prostate cancers; the 3+4=7 and, the 4+3=7. Importantly however, whereas the 3+4 is a low-risk cancer and tends to behave like the bogus G6 especially when it has 10 percent or less of pattern 4 disease — although the exact amount of pattern 4 to be significant is yet to be determined, the 4+3 behaves more like the high-risk Gleason 4+4 and, should be considered for treatment.
The PSA test
In order for the PSA prostate cancer screening test to be of health benefit it should be both highly specific and, highly sensitive for detecting ONLY the potentially lethal prostate cancers. However, the PSA is neither specific (it fails to detect just one tumor type — it is positive in some breast cancers and other conditions) and, is highly insensitive for detecting only the 15 percent or so of potentially deadly prostate cancers. Even the many available alternative biomarkers such as PSA derivatives like the percent free PSA and, PCa3, and others as well as genome tests, are not foolproof. Although also not dependable, the PSA density can be somewhat useful as a screening tool while monitoring serial PSAs for any upward trending may help as an indicator for additional review.
The PSA story
The PSA was discovered by Ablin in 1970. Using transcripts of the minutes recorded during the FDAs Immunology Devices Advisory Panel Meetings, Ablin and Piana (The Great Prostate Hoax) detailed a very dodgy FDA approval process for the PSA. Despite a standard FDA approval resting primarily on whether a device is “safe and effective”, the highly inaccurate PSA and its very high FALSE POSITIVE RATE was given FDA approvals in 1986 and, in 1994.
The highly unreliable PSA
Although marketed as “potentially life-saving”, the PSA blood test is highly unreliable. In fact, it is associated with a 78 percent false positive rate; although labelled as specific, it is NOT cancer-specific; cannot distinguish between lethal cancers, non-lethal cancers and benign prostate disease; there is no specific level that signifies a potentially lethal cancer; leads to the detection of mainly benign prostate diseases and Gleason 6 pseudo-cancer; its limits of 0–4 ng/ml as being “normal” are artificial; is commonly NOT the same result on repeat studies as it fluctuates normally; can be artificially raised or lowered by several processes without a cancer being present; often rises with age as the prostate grows; is normally high with big prostates and, MOST IMPORTANTLY, commonly fails to indicate the presence of the15 per cent or so of potentially lethal high-grade prostate cancers with significant amounts of pattern 4 and or, 5 disease as these cancers often make little or no PSA. Furthermore, should an elevated PSA lead to a significant prostate cancer being detected, the elevated PSA is commonly caused by the enlarged benign portion of the prostate and NOT the cancer.
The other components of PSA-based screening
1. The DRE (digital rectal exam)
The DRE is a finger examination of the prostate that has the same accuracy as a coin-toss. Performing this feeble test every few months during so-called prostate cancer surveillance makes no scientific sense; can be very uncomfortable; is especially unreliable for detecting the potentially deadly 15 percent or so of high-grade cancers early and, the examination is open to errors of interpretation and concerns for, “feeling something”, sensing a “nodule” or, feeling “unevenness” (asymmetry, which is normal). Terms often used by urologists simply to create confusion and doubt and, push men towards unneeded but money-making evaluations.
2. The ultrasound-guided prostate needle biopsy
The “standard” ultrasound-guided, 12-core needle biopsy of the prostate to try and detect prostate cancer is both highly unscientific and, highly unreliable. Not only is the trans-rectal ultrasound part of the study blind in that it is unable to “see” areas of high-grade prostate cancer within the prostate (nor is the 3D color doppler able to detect only high-grade cancer) but, despite the knowledge that prostate cancer often develops in more than one area of the prostate and or, at different times (not unlike bladder cancer), this blind needle biopsy “test” samples randomly only some 0.1 percent— 0.3 percent of the total prostate to leave one absolutely uninformed about the 99 percent rest of the prostate — especially so for the anterior portion of the prostate. Additionally, this highly inaccurate biopsy test is also responsible for all of the confusion related to so-called prostate cancer upgrading and progression. Because, prostate cancers can develop in some one to five different areas of the prostate because of a “field change” and, at different times it is easy to understand why the 12-core needle biopsy sampling randomly only about 0.1 percent of the prostate simply doesn’t reflect what is going on inside the prostate.
3. Pathology and x-ray reports are not foolproof
With this background of inaccuracy and unreliability for prostate cancer detection, the discovery that the pathology and x-ray reports are not always foolproof is also concerning. Your biopsy specimens are read by a pathologist who, like his or her radiology colleagues reviewing imaging (X-ray) studies — and, any other physician having to make a judgement call — can make incorrect diagnoses because of inadequate knowledge and or, because of errors-of-interpretation. This is especially so for diagnosing prostate cancer because of the complexity of the Gleason grading and scoring system. Here, pathologists have to judge tumor aggressiveness based upon growth pattern appearances under the microscope and then combine estimates of the two most common patterns of growth seen (each arbitrarily graded 1–5 with 5 being the most aggressive) on the slide for a Gleason score. Since the biopsy reading is very dependent upon the individual ability of the doctor, incorrect judgements of cancer grade, Gleason score, cancer amount (volume), core length and or, whether a cancer is even present, are possible. Furthermore, although other background findings such as atypical small cell acinar proliferation (ASAP), high-grade prostatic intraepithelial neoplasia (HGPIN) and perineural invasion are often recorded, by far the most important feature of the biopsy report is whether or not significant amounts of high-grade (4s and 5s) prostate cancer have been identified as these cancers can benefit from treatment. However, because of these possible errors-of-interpretation, getting prostate biopsy findings confirmed by a recognized leader in prostate cancer pathology is recommended highly.
The best prostate cancer screening and detection tool is the 3T MRI
To date, the newer versions (versions 3–5) of the 3T MRI (but only in the right hands) are the most reliable (almost foolproof) devices for screening and detecting the 15 percent or so of potentially deadly high-grade prostate cancers. Unlike the current “standard” screening and detection methods, the 3T MRI evaluates the WHOLE of the prostate, can ignore the bogus G6 cancer and, based upon imaging details in a properly conducted study, able to identify reliably with PIRADS 4 and 5 features, almost all high-grade cancer anywhere within the prostate — features which also make it an ideal surveillance tool to monitor low-risk 3+4 cancers. Any high-grade areas identified can then be targeted for needle biopsy under real-time 3T MRI for confirmation of disease as only these particular prostate cancers demand detection and treatment — a process far more accurate than the popular MRI/ultrasound fusion technologies in play currently in many urologists’ offices.
Joe Busch MD, prostate MRI specialist, Chattanooga, Tennessee (personal communication) www.drcradiology.com/
PSA testing and screening — a bad prescription
The PSA test is a highly unreliable tool when used to screen for prostate cancer because it commonly results in men being steered towards unnecessary evaluations and unneeded treatments. A huge problem that did not escape the attention of the USPSTF (United States Preventive Services Task Force) who warned that for PSA-based screening and the treatment of screen-detected cancers, “the benefits do NOT outweigh the harms”.
There are several reasons behind this unending public health tragedy:
- Despite a very high false-positive rate, the PSA was FDA approved in 1986 for use as a tool to monitor the status of men already diagnosed with prostate cancer. In 1994, it was approved for use as a screening aid for diagnosing cancer but quickly misused by physicians as a tool for wholesale prostate cancer screening.
- Surprisingly, the very prostate cancers that demand detection often go undetected because the all-important potentially lethal high-grade cancers commonly do not produce much if any PSA. Instead, a so-called abnormal PSA level usually leads to a risky and unreliable prostate biopsy which then leads to the detection of mostly benign prostate disease and or, the Gleason 6 pseudo-cancer.
- Adding further fuel to the early detection-to-treatment prostate cancer debacle is the finding that the ubiquitous Gleason 6 was misrepresented as a cancer for many years. Klotz reviewed the data surrounding the Gleason grade 3 (as in the Gleason 3+3=6 “cancer”) and concluded that, based upon clinical and molecular biology evidence, it lacked the hallmarks of a cancer. This shocking discovery meant that men treated for their Gleason 6 disease were survivors of a treatment they never needed and, not survivors of the bogus cancer.
- Equally revealing is the discovery that contentious therapies like radical (robotic) surgery may not be what they seem — safe and effective. This ill-conceived and dangerous procedure simply evolved as standard-of-care without any objective testing and, according to Horan,“without proof of life-extension in man or animal that would satisfy the committee on medical experimentation at Nuremberg”. In step with this stunning conclusion about prostate cancer surgery, Robert Aronowitz, an internist and medical historian in his publication, “Screening for Prostate Cancer in New York’s Skid Row: History and Implications”, underscored once more the many concerns about prostate cancer screening, treatment safety and effectiveness and, determined that “our screen-and-treat paradigm in prostate cancer is evidence-challenged”. A point highlighted by Ablin and Piana who stated,“the ill-use of a prostate cancer test has systematically ruined the lives of millions of American men”.
Does PSA testing save lives?
No. The PSA fails to save significant numbers of lives and, urologists already know that. They underscored this fact by concluding in their article that, “PSA-based screening results in a small or no reduction in prostate cancer specific mortality”.
Clearly, when the PSA is used to screen for prostate cancer its extraordinary high rate of false positives simply ensures that nearly 80 percent of men with an elevated PSA level will be funneled towards highly unreliable, unnecessary and, risky evaluations. Especially, when the emotionally-charged cancer word is unloaded upon them. What’s needed desperately is a simple biomarker that will detect reliably, only those with the potentially deadly forms of prostate cancer early enough for possible curative treatment. Till then, prescribing the highly unreliable PSA test for prostate cancer screening remains bad health advice as it simply exposes countless numbers of men to the harms of over-diagnosis and over-treatment.
A. Horan, The Big Scare
Final Update Summary: Prostate Cancer: Screening - US Preventive Services Task Force
Clinical summaries are one-page documents that provide guidance to primary care clinicians for using recommendations in…
Bert Vorstman BSc, MD, MS, FAAP, FRACS, FACS
Originally published at urologyweb.com on March 30, 2019.