When standard-of-care is an excuse for licensed medical malpractice
Are you getting trustworthy prostate cancer information? The terms standard-of-care, medical practice guidelines, FDA approved and, covered by insurance certainly seem very reassuring. But let’s see if some of these long-held beliefs about prostate cancer testing and treatment are dependable or whether they are simply untrue.
Curious Dr. George: Most people with prostate cancer live a long and healthy life. But some die, with or without treatment. It can be a confusing disease. To what extent are American men and physicians receiving trustworthy information about prostate cancer?
The term prostate cancer.
Belief – All prostate cancers are deadly.
Evidence against the all-inclusive prostate cancer label – Prostate cancers are not all equally deadly. In fact, it’s mostly the 10 to 15 percent of high-grade, aggressive prostate cancers that are responsible for the 30,000 or so U.S. deaths annually.
Bottom line – The vast majority of men diagnosed with prostate cancer do not die of it. Furthermore, not only is the 10-year survival about the same whether treated or not but the 15-year survival rate, irrespective of treatment option, is about the same.
Prostate specific antigen (PSA) blood test.
Belief – The PSA test leads to early prostate cancer detection, early treatment and life-extension.
Evidence against PSA testing – The PSA has a false-positive rate of 78 percent because it is neither specific to the prostate or specific to prostate cancer; its so-called cut-off value of 0-4 n g/ml is an arbitrary and misleading metric; a PSA above 4 does not mean a diagnosis of prostate cancer; large prostates commonly generate high PSAs; the PSA value can be artificially raised or lowered without a cancer being present or progressing; the PSA cannot distinguish between aggressive and non-aggressive cancers; lowering the PSA does not lower a risk of cancer and, the subset of high-grade, aggressive and potentially deadly prostate cancers may produce little to no PSA and can go undetected. Incomprehensibly, although the reliability of the PSA was concerning from the outset, the FDA (Food and Drug Administration) approved the PSA test for prostate cancer screening in 1994. Unsurprisingly, in 2009 urologists clinical studies determined that PSA testing failed to save significant numbers of lives. More damning, the USPSTF (United States Preventive Services Task Force) gave PSA-based prostate cancer screening a “D” grade in 2011 concluding that, “the benefits do not outweigh the harms”. Shamefully, after pressure from self-interest groups the USPSTF “D” grading was watered-down to an ineffectual “C” warning in 2018.
Bottom line – PSA-based screening – includes the inaccurate digital prostate exam or digital rectal exam (DRE) – is highly unreliable, risky and fails to save significant numbers of lives. In fact, many cancers are detected by chance during evaluation for an elevated PSA as the PSA was generated by the BPH and not the cancer. Currently, there is no blood or urine test that can detect just high-grade prostate cancer reliably.
The ultrasound-guided prostate needle biopsy.
Belief – That an ultrasound-guided prostate needle biopsy can reliably detect a potentially deadly prostate cancer.
Evidence against the ultrasound-guided prostate needle biopsy – 1. Prostate cancer is commonly a multifocal disease – meaning that areas of cancer can arise in several different areas of the prostate at the same time or, later. Yet, so-called standard practice for detection calls for the use of an ultrasound, which can’t see the cancer and then randomly and blindly biopsy the prostate 12 times with a needle to evaluate whether or not a cancer is present. When the volume of these 12 needle cores is measured against the volume of an average prostate, only about 0.1 percent of the prostate ends up being sampled. It also means that the clinical state of the 99.9 percent of the un-sampled prostate remains unknown. Even if 120 biopsies were taken (10 times the standard number of 12) you would still be clueless about 99.0 percent of the prostate. 2. There are two techniques for prostate biopsy: transrectal or transperineal (with or without a template). The transrectal approach is riskier than the transperineal and is associated with potentially serious complications of sepsis and bleeding. 3. The concern about false negatives (missing cancers) is hardly surprising when only 0.1 percent of the prostate is sampled. The transrectal approach has recorded a false negative rate of more than 33 percent. On the other hand, others have claimed to find 6 percent more cancers using the transperineal route. Possibly because of the compressive effects on the prostate and the angle at which the transperineally placed needle enters the prostate.
Bottom line – The ultrasound-guided needle biopsy test is risky and embarrassingly unscientific because of its egregious sampling error. The perineal approach is less risky but equally unscientific. Additionally, there is no hard evidence that either technique detects significant numbers of the 10-15 percent of the potentially lethal high-risk tumors. However, the best current screening tool to detect significant cancer anywhere in the prostate is the non-contrast MRI conducted by a radiologist with expertise in MRI prostate imaging. Areas judged to be consistent with PI-RADS four or five disease on the MRI are suggestive of potentially lethal high-grade disease and can be confirmed with an MRI-guided targeted biopsy.
The Gleason grade and score.
Belief – A pathologist’s interpretation of what is judged to be a certain grade of cancer under the microscope is reliable.
Evidence against Gleason grading reliability – The Gleason grading and scoring system is complex and relies overly on a pathologist’s knowledge and interpretive skills for estimating what grades of cancer they believe to see under low-power microscopy. Because of potential errors of judgment, grade misclassifications and disagreements amongst pathologists are common – underscoring a profound lack of reproducibility of the Gleason system.
Bottom line – Patients can never be absolutely sure of their prostate cancer grades and scores. Getting a second opinion from an experienced prostate cancer pathologist and undertaking a screening non-contrast MRI of the prostate with an expert is appropriate.
The Gleason grade 3 and the 3+3=6 “cancer”.
Belief – The Gleason grade 3 (in the Gleason 3+3=6) is a “cancer”.
Evidence against the Gleason grade 3 being a cancer – Initially, the Gleason grade 3 appearance under low-power microscopy was thought to be consistent with an early low-grade, low-risk cancer. However, since then, both the clinical evidence and the fact that the genetic pathways enabling cancer development and spread are turned off indicate that the Gleason grade 3 lacks the features of a cancer.
Bottom line – The Gleason grade 3 fails to behave as cancerous since it is not a cancer. Shamefully, the grade 3 (3+3=6) is still labeled as a cancer, scaring untold numbers of patients towards unnecessary investigation and harmful treatment. Rather, the grade 3 disease appears to be simply a benign feature of aging.
Imaging for the staging of prostate cancer.
Belief – That bone scans, ultrasounds and CT scans can determine whether a cancer is localized or has spread.
Evidence against bone scans, ultrasounds and CT scans for staging – Bone scans, ultrasounds and CT scans are quite insensitive for detecting small volume cancer spread making their use in staging unreliable. Underscoring this concern is the fact that prostate cancer cells have been found in the bone marrow of patients with so-called localized disease. These metastases may begin when high-grade cancers are as small as 0.25 mm in size and barely detectable within the prostate.
Bottom line – Staging of prostate cancer using bone scans, ultrasounds and CT scans is unreliable due to their insensitivity. The PMSA PET/CT scan and the whole body diffusion MRI studies have greater reliability for detecting small-volume spread to lymph nodes and bones.
Prostate cancer surgical “treatment”.
Belief – That cutting out prostate cancer – whether open or robotically gets rid of it and “saves lives”.
Evidence against surgery – H.H. Young M.D. claimed early diagnosis, cure and “the remarkably satisfactory functional results furnished” from his surgical technique. In contrast, he gave zero evidence for early diagnosis or cure, two patients died and the other two were left with lifelong urinary leakage. And, when robotics entered the business of surgery not only was the device given an FDA approval without demonstrating clear benefits but the FDA’s fallacious 510(K) process was then manipulated to permit use of the tool in radical prostate surgery. Again, without sufficient evidence for safety or benefits. Unsurprisingly, the robotic prostatectomy has a similar incidence of residual cancer (positive margins occurred in 11- 48 percent of patients) and a similar incidence of impotence and incontinence to open surgery. These complications are common and typically managed with radiation, counseling and rehabilitation programs or, implantable devices for ongoing limp and leaking issues. The breakdown of these gadgets often results in more surgery, costs and suffering. In fact, the number of complications associated with the robotic device is highlighted in the FDA’s MAUDE (Manufacturer and User Facility Device Experience) site which recorded a great increase in adverse events. Irrationally, radical prostatectomy is still considered standard-of-care despite physicians concluding in 2012 that surgery failed to save significant numbers of lives. And, despite the evidence against surgery, the SPCG4 article and its conclusion “Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer”, is often quoted by urologists to support their opinion that radical prostatectomy saves lives. Aside from this work recording a substantial number of impotence and incontinence complications, the study is also flawed because of the commingling of participants with various Gleason grades and scores (both well differentiated and moderately well differentiated), unknown tumor volumes and the arbitrary use of anti-androgens in others – issues that can skew results. Additionally, the relatively short follow up time for this study (15 years) is troubling since the particular prostate cancers that the researchers targeted grow very slowly. For the low Gleason score/low-risk/well-differentiated, grade 1 tumor a mean cell doubling time of about 577 ± 68 days has been recorded. This figure means that it can take some 40 years or more from the time of cell mutation for the cancer to reach a diameter of 1 cm and be big enough to be felt on manual prostate examination. Clearly, such a slow cell division rate and a median follow up time of 12.8 years can only deliver a semblance of cure.
Bottom line – Cutting out prostate cancer whether by robotic or open techniques is unsafe and fails to save significant numbers of lives. Worse still, life extension has not been demonstrated for any focal or whole-gland prostate cancer treatment options. In part, because most, if not all, studies are flawed by the inclusion of participants with the bogus Gleason 6 “cancer”, incorporating patients with dissimilar Gleason grades, scores and tumor volumes, reliance on insensitive staging methods and, arbitrarily treating others with testosterone suppression.
Active surveillance for low-risk prostate cancer.
Belief – That by using 6 monthly PSAs, 12 monthly DREs, 12 monthly biopsies (a random 12-core) and maybe a 12 monthly MRI urologists can assess if a low-risk prostate cancer was progressing and required treatment. Urologists initiated this program for monitoring low-risk disease after appreciating the facts that most prostate cancers grow slowly and that the treatments were often worse than the disease. Enthusiastic support also came from the NIH.
Evidence against active surveillance – 1. PSA testing (and all other tests incorporating the PSA), DREs and 12-core biopsies (whether transrectal or transperineal) are highly unreliable as detailed above. 2. A prostate cancer diagnosis was likely established on the basis of a 0.1 percent random and blind sampling of the prostate. The follow up biopsy is likely done in exactly the same way. Clearly such an unscientific process can fail to detect a cancer, is unable to target reliably the original cancer and determine if the original cancer has “progressed” or, whether the cancer now detected was already present but missed by the previous biopsy. 3. Since non-contrast MRIs of the prostate (by a radiologist experienced in prostate MRI imaging) are able to examine the whole prostate and reliably identify the 10-15 percent of potentially lethal cancers their use has become more common. However, not all MRI’s are equal. Although MRI-guided targeted biopsies have been recorded as being dependable, most prostate needle biopsies are not undertaken using MRI-guided targeted techniques but by urologists using “fusion” studies. There are a number of concerns associated with the reliability of this fusion method. The MRI is commonly undertaken by a radiologist of unknown experience, knowledge and interpretative ability for PI-RADS findings – PI-RADS 4 or 5 changes on the MRI may reflect potentially lethal disease. However, this PI-RADS classification, like the Gleason grading and scoring system, is complex and has concerns for errors of interpretation. Additionally, the quality of the MRI study generated can be impacted by the radiologist’s particular study methodology, the particulars of the MRI machine and its software. Then, this previously recorded MRI study is “fused” with the ultrasound study on the day that the prostate biopsy is undertaken. Now, there are additional concerns relating to the type of ultrasound machine to be used and the ability of the urologist to interpret the images. Once “suspicious” areas are “identified” with this fusion method they can be targeted for biopsy. Absurdly, many urologists will add a random biopsy sampling 0.1 percent of the prostate to the targeted biopsy of the high-risk area located in the fusion study. This additional biopsy may only increase the risk of complications and the detection of non-lethal disease. Also bothersome, although MRI-guided targeted biopsies of PI-RADS 4 and 5 areas by radiologists may be more reliable, the fusion technique keeps the biopsy (and revenue) in the hands of urologists. 4. The definitions used to determine “progression” of low-risk disease are variable, unreliable and also impacted by laboratory and observer error – PSA level, PSA velocity or density, clinical staging, DRE, biopsies, Gleason grades and scores, tumor volumes and the number of positive cores and core lengths – none truly reflect what’s happening in the entire prostate. 5. PSA testing and surgical treatment do not save significant numbers of lives. 6. Whether you are treated or not the 10 year survival is about the same.
Bottom line – Clearly, misinterpretations about the presence or absence of cancer, stability of a low-risk cancer or the “progression” of disease are inevitable because of multiple inaccuracies. The potential benefits of active surveillance for low and moderate risk prostate cancer and the saving of significant numbers of lives because of so-called “timely” identification of disease progression have not been supported by hard data. This is not surprising when a number of highly unreliable tests are conflated to generate an unreliable endpoint before initiating a treatment option for which there is no evidence that significant numbers of lives are saved.
Why prostate cancer information is untrustworthy.
PSA-based testing and prostate cancer surgery are both risky and fail to save significant numbers of lives. How then, did the standard-of-care dogma about prostate cancer testing and treatment become so disconnected from the clinical evidence?
Meta-researcher John Ioannidis M.D. discovered the likely cause of this uncoupling of treatment beliefs from the evidence after reviewing multiple healthcare papers. He concluded that “most published research is false”. False, because most studies were commonly not founded on sound scientific principles and corrupted by errors of judgment, approximations, opinions, assumptions and conflicts-of-interest. Making this “research information” more suspect was the inevitable manipulation of study design and results by sponsoring organizations to produce “facts” supporting their biases.
Reliable healthcare information can only be developed from data sourced from studies delivering irrefutable and reproducible results. In contrast, much of the material used to develop the guidelines for prostate cancer management came from very poorly designed studies and beliefs. An all too common junk science that results in prescriptions for care that are untrustworthy, commonly exploitative and make a mockery of the Hippocratic Oath.
The Great Prostate Hoax by R. Ablin and R. Piana.
The Rise and Fall of the Prostate Cancer Scam by A. Horan M.D.
This article is dedicated to Anthony Horan MD, a urologist and author (The Rise and Fall of the Prostate Cancer Scam) who fearlessly challenged the culture and the business of prostate cancer. He was always on the right side of what should never have been a controversy. Sadly, the prostate cancer testing and treatment industry is a 32.7 billion dollar market for which there is no hard evidence that significant numbers of lives are being saved.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.