The Imperfect PSA,
the Fraudulent Robotic Prostatectomy
and Medical Ethics.
The US Preventive Services Task Force Weighs In
Bert Vorstman MD, MS, FAAP, FRACS, FACS
Background
The controversy surrounding the prostatic specific antigen (PSA) is not so much about this blood test being an imperfect marker for prostate cancer but much more about the very negative downstream issues associated with evaluation and treatment of prostate cancer detected because of this marker. This very basic but well-known fundamental healthcare concern represents a major ongoing ethical challenge for all physicians and is the reason behind the US Preventive Services Task Force (USPSTF) upholding its original grade D category for NOT recommending the total PSA test for use as a screening tool for prostate cancer. In that report, results from pooled data showed that PSA-based screening with the total PSA and treatment with prostatectomy, when compared to watchful waiting, was associated with:
> harms related to false-positive test results,
> overdiagnosis and overtreatment because of detection of low-risk cancers,
> treatment harms most applicable to prostatectomy,
> no statistically significant effect on prostate cancer-specific mortality in most trials,
> even a small possibility of benefit outweighs the known risk of harms.
The first concern regarding unnecessary testing is aimed at the imperfect total PSA causing significant numbers of men with false positive PSAs to undergo unnecessary and risky prostate biopsy evaluation. This problem can be corrected in part by focusing more on the testing of concerned men as well as those in known risk groups and by testing PSA derivatives and following PSA kinetics. Importantly, this approach with measuring PSA derivatives may help identify the 15-20% of asymptomatic men who have a normal total PSA (false negative) but have prostate cancer.
The next major problem of lasting harm and failure to reduce prostate cancer deaths significantly is directed for the most part squarely at the radical surgery/robotic prostatectomy camp, the original member of the primary treatment options for prostate cancer. The USPSTF has been one of the few organizations not intimidated by traditional surgical philosophy and surgeons regarding their continued misguided support for whole gland excision in the absence of corroborating data. In fact, the USPSTF reports that the current surgical excision treatment of screen-detected prostate cancer is not the answer and better treatment options are needed. Clearly, despite surgeons trying to legitimize the place of prostatectomy for over 100 years, it is obvious to some that this operation needs to be abandoned finally. Instead, a review of alternative treatments as well as minimally invasive and focal options is in order, if only to minimize the significant lasting harm associated with the surgical/robotic treatment for localized prostate cancer. Sadly however, surgeon’s egos and revenue appear to trump medical leadership and ethics.
The Imperfect Total PSA
Although a total PSA can lead to both false negatives (a “normal” PSA but have cancer) and false positives (an “abnormal” PSA but have no cancer), only the prostate needle biopsy and pathological examination can determine the presence of a cancer.
> there is NO SAFE PSA level below which a man can be assured that he does not have prostate cancer, and a decision on what level PSA endpoint to use before considering a prostate biopsy can be very difficult.
> the PSA is not even specific to the prostate.
> the PSA can be normal but one can still have a cancerous prostatic nodule detected during a digital rectal examination (DRE).
> the PSA can be normal as well as the DRE be normal and you can still have prostate cancer.
> the PSA can be abnormal, the DRE abnormal and there may be no cancer.
> the total PSA is about as accurate as a coin toss, or worse, for suggesting a possible cancer.
> an elevated PSA reflects more commonly the benign enlargement component of the prostate or BPH and/or associated, asymptomatic inflammation called prostatitis.
> for many men, the small amount of prostate cancer found because of an elevated PSA was simply due to the benign enlargement of the prostate and not a reflection of the small amount of often insignificant, coexisting cancer.
> the PSA is unable to distinguish significant prostate cancer from insignificant prostate cancer.
> the PSA under 10 ng/ml does not correlate well with prostate cancer in presence or amount.
> a man with a “normal” PSA under 4 ng/ml will have an approximately 15% chance of having prostate cancer.
> a man with a PSA between 4-10 ng/ml will have a 30% chance of having cancer.
> a man with a PSA of over 10 ng/ml has a 40 -70% chance of having prostate cancer.
> there are 4 classes of medicines well-known to artificially lower your PSA (thiazides, 5 alpha reductase inhibitors, NSAIDS and statins) and probably without protective value. Trying to lower your PSA by any means including antibiotics, is a valueless exercise.
> laboratories may also give you a spurious PSA result as well as different laboratories having different methodologies for PSA estimation and different PSA limits.
> there are several conditions that can falsely raise your PSA and you should not have your PSA estimated the morning after sexual activity, after a prostate exam or immediately after a lower urinary tract infection.
> high-risk or aggressive prostate cancers may produce little if any PSA rise, even with prostate cancer progression. The upgrading of residual prostate cancer to a more aggressive cancer form may occur after any treatment option.
> the PSA is reliable generally only when used for post-treatment monitoring.
Minimizing PSA Imperfection through Derivatives and Kinetics
The perfect prostate cancer marker (or any marker used for disease screening) should be able to detect significant disease in at least 80% of asymptomatic but afflicted people. The total PSA never reaches even close to this ideal detection rate. Lowering this imperfect PSA and its arbitrary cutoff level from 4 ng/ml to 2.5 ng/ml and attempting to detect disease at an even earlier stage is more likely to raise the number of men undergoing risky prostate biopsies as well as the detection and treatment of more insignificant prostate cancers.
Rather than using the imperfect total PSA, the use of PSA derivatives (free and percent free) and kinetics may help to lower the incidence of false positive PSAs as well as false negatives.
> measuring the total PSA as well as the free PSA to determine the percent free PSA and the probability of prostate cancer on several occasions as well as ensuring that the PSA is not estimated until 24 hours after sexual activity or a DRE.
> determining the PSA density or dPSA; a dPSA over 0.15 is believed to be significant.
> determining the PSA velocity and a PSA increase by 0.75 ng/ml/y is believed to be significant.
> determining the PSA doubling time which is the length of time in months for a PSA to double based upon exponential growth with a shorter (but faster) doubling time having a poorer outlook.
> age specific PSA ranges using tables suggesting increasing PSA ranges for advancing age.
> evaluating the PSA after a 3-month course of finasteride to see if the PSA drops by about 50%; if so, it is thought that the chances of prostate cancer are diminished.
> performing the PCa3 test which involves a prostatic massage and mRNA analysis of the seminal fluid washed out in the initial urine sample after the massage and may be useful when the information is combined with the PSA derivatives.
Refining Criteria for PSA Testing
Rather than the meritless wholesale screening of all men for prostate cancer which leads to a diagnosis of prostate cancer in less than 5% of men tested (and probably mostly with localized insignificant disease), consideration should be made for testing only:
> concerned, healthy men (should have at least 10-15 years or so of anticipated active life and without significant comorbidities such as a cardiac history or significant diabetes which can impact survival) or, those men in the following categories with known increased risk of developing or having prostate cancer,
> abnormal prostate examination (a very subjective test and simple asymmetry of the prostate is not a valid reason for a biopsy).
> low serum testosterone and possibly, in particular, the percent-free testosterone.
> family history of prostate cancer.
> African heritage.
> obesity.
> previous microfocal cancer or precancerous findings. Although recommended, routine PSA evaluation every 6 months or so while undertaking active surveillance for known small volume, low risk prostate cancer or precancerous findings such as atypical small cell acinar proliferation (ASAP) or multifocal high grade prostatic intraepithelial neoplasia (HGPIN) is not accurate for determining progression and cannot replace prostate needle biopsies every 1-2 years.
The Fraudulent Place of Radical Surgery/Robotic Prostatectomy
Coupled with the imperfect PSA as a screening test for prostate cancer is an even greater problem, that of the fraudulent place of the scientifically unproven, high risk, irreversible radical surgical/robotic procedure as a treatment option for localized prostate cancer. In fact, the
USPSTF paper reported that for nerve-sparing approaches using laparoscopy or robotic techniques, they “ found no pattern suggesting that more recent studies reported different risk estimates from older studies”. Therefore, like traditional prostatectomy, robotic prostatectomy appears to be a bigger “cancer” risk by far to a man’s quality of life than the actual cancer in the prostate of many men for the following reasons:
> no significant curative life extension.
> small to NO reduction in prostate cancer-specific mortality in most studies.
> relative absence of well-designed, long-term, scientific, randomized clinical trial (RCT) and evidence-based medicine (EBM) studies and data for prostate cancer treatment.
> deceitful practice of misconstruing clinical information as evidence-based data.
> deceitful practice of claiming FDA approval whereas the radical surgical/robotic procedure was simply given a pass by the FDA and never scrutinized scientifically for risk or reward.
> pervasive, unchecked and unconscionable overtreatment of insignificant cancer.
> high rate of lasting harm and negative impact on quality of life (QoL) because of incontinence, impotence, shortened penis and many other issues including mortality, cardiac and vascular.
> misinformation regarding the neurovascular bundle and nerve-sparing to maintain potency as the nerves, at best, only follow the vascular bundle in 50% of cases and cannot be identified.
> high rate of secondary surgeries to correct incontinence, impotence, bladder neck contracture and other complications.
> 20-40% incidence of residual untreated prostate cancer after high-risk surgery.
> deceitful practice of recommending watchful waiting or radiation for residual cancer after first recommending, then performing, the scientifically unproven prostatectomy.
> deceitful practice of recommending debulking for local control of advanced prostate cancer.
> deceitful practice of implying that surgery is a significantly better treatment for younger men.
> deceitful practice of implying that surgery is better for aggressive prostate cancers.
> deceitful practice of implying that compared to traditional prostatectomy, robotic prostatectomy
diminishes lasting harm and lowers prostate cancer mortality.
> deceitful practice of implying curability and life-saving.
Prostate Cancer Statistics
> the incidence of prostate cancer is slowly rising, probably because of unchecked PSA testing.
> autopsy studies have recorded a high percentage of incidental prostate cancer with advancing age (about 70% of 90 year-old-men have latent prostate cancer). These incidental or latent cancers (rare in other organs) never impacted these men, underscoring the point that most prostate cancers are not a common cause of death.
> the advent of the PSA in the 1990s has resulted in the diagnosis of an ever increasing incidence of prostate cancers, mostly insignificant.
> the lifetime risk of a man being diagnosed with prostate cancer (cancer of unknown significance) is now about 1 in 12.
> in 2010, the census population of US males over 40 years of age was 67,500,444; the number of males diagnosed with prostate cancer in that year was about 220,000 or some 0.32% of men (but cancer of unknown significance), while the number of men who died that year from prostate cancer (according to unreliable death certificates) was about 29,000. These deaths resulted in about 9 years of lost life.
> only about 1 in 380 men over 50 years of age with prostate cancer picked up because of an abnormal total PSA will die from his prostate cancer.
> 50 men need to be treated for their prostate cancer (that often was insignificant and never going to impact them) in order to reduce one prostate cancer death. In other words, the few killer
prostate cancers are outweighed by far by the majority of non-killer prostate cancers.
> in men with low-risk prostate cancer, the risk of prostate cancer specific mortality is only about 9% whereas the mortality risk from a cardiovascular event was 18% and from all other competing causes was 25%. For intermediate-risk prostate cancer, the risk of prostate cancer specific mortality is about 19% and similar in incidence to that of cardiovascular events.
> survival rates for prostate cancer have been improving, not because of surgical/robotic treatment, but because of the detection of insignificant prostate cancers as well as the advent of more advanced general health care.
> the prostate cancer cell is generally very slow growing (on average divides every 475 days or between 380-570 days). This means many prostate cancer cells take close to 2 years to divide, so prostate cancer recurrences can take 20 years or so to manifest and therefore talk of zero PSA progression or talk of prostate cancer survivors at 5-10 years after radical surgical/robotic treatment is absolutely meritless.
> the average age at diagnosis of prostate cancer is 67 years and some 75% of diagnoses are made after age 65.
> for MOST prostate cancers, the word “cancer” is a MISNOMER as many prostate cancers are insignificant and have a slow prolonged natural history and without impact on many men.
More Reality Checks
The prostate cancer arena is a business world loaded with financial incentives, inaccuracies, subjectivity and observer issues, purposeful misinformation, falsehood, ludicrous self-serving definitions of treatment success and treatment complications, worthless 5-10 year study information, powerful egos, bias and dilemmas where this alchemy of imperfection is miraculously distilled, refined and “spun” into “information” and “results”. In reality, there is a profound lack of reliable information as there is a relative absence of well-designed, long-term, scientifically-run, randomized clinical trials for prostate cancer treatment to provide reliable evidence-based medicine data. Instead, much of the information available comes from a preponderance of self-serving clinical studies misconstrued as data. In addition to these clinical studies there are so-called databases and registries in use for several of the prostate cancer treatment options like hifu (hot registry), cryoablation (cold registry) and radiation (radiation registry). However, there is no database or registry for radical surgery/robotic prostatectomy. The keeping of these databases is laudable but the “information” here is unreliable for the following reasons:
> there is a constant refinement of technology and software making results for a particular treatment, or even between different treatments, incomparable.
> there is no accountability usually for the significant issues of observer/operator error or subjectivity in interpreting pathology or imaging studies.
> there is a total lack of uniformity on definitions for treatment success and complications.
> there exists commonly a flagrant conflict of interest issue with members of the same department or institution interpreting results as well as providing second opinions.
> virtually all treatment studies are filled with a mixed bag of prostate pathology where men with low volume, low-risk prostate cancer disease have been included with those that have high volume, high-risk disease but all with the same stage. Therefore, studies can report good results simply because they were loaded with low volume, low-risk and commonly insignificant disease.
More importantly, despite this assemblage of information, urologists are unable still to identify reliably the subset of prostate cancers that truly demand treatment. What may be significant and somewhat predictive of biological behavior is tumor volume of at least 0.5 mls or so possibly detected through multi-parametric 3T MRIs as well as tumor grade identified through needle biopsies of the prostate targeted to these suspicious areas. Although prostate cancer tends to be multifocal, treatment of just the biggest and usually significant “index” lesion through a focal therapy may prove to be a better treatment than whole gland excision especially if only to minimize the incidence of complications and lasting harm arising from the traditional but meritless radical surgery/robotic prostatectomy.
Physician Moral Conflicts
Physician medical professionalism, bounded by the Hippocratic Oath as well as a medical Code of Ethics, serves to delineate the standard of expected physician ethical behavior. These dictums should be interpreted not as a guide for behavior but what is expected of physician behavior. In essence, it is for physicians to be the patient’s sincere advocate and to do no harm or injustice. All physicians have these unsigned, social and moral pledges with patients and society where the patient’s interests and welfare are paramount and safeguarded through trust, honesty, integrity, character, competence and obligation. Although these contracts are fundamental to ethical physician-patient relationships, infallibility is obviously not a tenet. However, what is very clear and constitutes divergence from these pledges and codes is not isolated infallibility but intent, such as intentionally misrepresenting or misleading a patient with misinformation or false claims.
Although these codes for expected physician behavior feature prominently in medical
organizations universally, they are not always fully embraced and this is especially so in the prostate cancer arena. Only but very rarely over the past 100 years or so that radical surgery for prostate cancer has been practised and generated its significant list of complications and harm has the conscience of urologists ever been pricked or our Code of Ethics ever resonated. The USPSTF clearly recognizes these negative issues and ethical concerns with the failure of prostatectomy to be legitimized scientifically, and challenges urologists once more to address and resolve these most fundamental of health care concerns.
> “no harm or injustice”: Here the perceived benefits of radical surgery/robotic prostatectomy are at complete variance with the prevailing clinical evidence in that there is lasting harm and no significant numbers of lives saved from prostate cancer. In fact, the clinical evidence available indicates that the risk of having an undetected prostate cancer is severely outweighed by the risk of its discovery and radical surgery/robotic prostatectomy treatment.
> “truth and honesty”: A core tenet in the medical Code of Ethics is truth and honesty and when misinformation or false claims are seen, heard or experienced repetitively and in clear disconnect from one’s ethical and moral pledges to codes of conduct, malintent is clear. There are no degrees of truth or honesty but the practice of half-truths, doublespeak and misinformation across all media formats, including medical marketing, has become quite acceptable and is without redress or penalty. Even reputable urology affiliate organizations like the various prostate cancer organizations and societies, prostate cancer support groups, hospital urology programs, Institutional Review Boards, insurance companies as well as the FDA have been too weak and intimidated by the urology establishment to challenge this crisis of misinformation on prostate cancer screening and prostatectomy treatment.
> patient “non-exploitation” is not a tenet in the Code of Ethics but should be, especially so for the prostate cancer industry where there is unbridled exploitation of a man’s undeserved fear of prostate cancer. This particularly reprehensible practice can be exercised mentally, physically or both.
i) psychological exploitation: Surgeons are well aware of the very severe emotional charge that the word “cancer” generates and instead of spending time for advocacy and counseling, some surgeons simply capitalize on a man’s vulnerable mental state and pander to feelings of hopelessness. That a man’s erroneous innate belief for “cure” is to have his prostate cut out and quickly is a chance for psychological exploitation by some surgeons with shameless opportunistic fostering of anxiety and doubt without conscience or integrity, and steer him towards the scientifically unproven prostatectomy.
ii) physical exploitation: This practice describes the pervasive and malignant medical practice of performing unnecessary treatments and or unnecessary ancillary procedures for the simple purpose of up-coding and revenue garnering. As such, the ever increasing over-treatment of men with insignificant prostate cancer is reaching epidemic proportions endlessly fueled by financial incentives and the business calling rather than the medical calling of medicine. This unchecked process has resulted in an enormous cost and public health issue.
Ethics, morality, character and discipline are neither optional nor interchangeable, and without a return to honesty and real data from evidence based medicine, the current muted interpretation of ethical pledges as well as the pseudo scientific support for the current status quo and acceptance for prostate cancer screening and prostatectomy by urologists is pure hypocrisy and guarantees a shameful legacy similar to that which occurred for the mutilating human experimentation that was called radical mastectomy.
Physicians, as well as urologists, are expected to have an unwavering duty to do only what is right and what is honest for their patients, and the disconnect between the radical surgical/robotic prostatectomy treatment for prostate cancer, the medical Code of Ethics, patient advocacy, standard of care, best practice, consensus-based medicine and informed consent is glaringly obvious. All physicians need to reconnect with the fundamentals of the pledges and codes that are at the core of their profession. In fact, the recent report by the USPSTF recommends once more for a better screening test than the total PSA and a better treatment option for localized prostate cancer than the prostatectomy because of the lasting harm and failure of this treatment to reduce prostate cancer deaths. In doing so, the USPSTF indirectly questions urologists’ connection to the Code of Ethics.
Finally, for now, all men must be their own advocates and ensure that they become truly informed and empowered about PSAs, prostate cancer and minimally invasive and focal treatment options as well as make great efforts not to become a victim of surgical care.
Bibliography
Books
1. The Big Scare – the business of prostate cancer, Anthony Horan, MD
2. Surviving Prostate Cancer without Surgery, Bradley Hennenfort, MD
3. The Male Lumpectomy, Gary Onik, MD
4. How We Do Harm, Otis Brawley, MD
5. Worried Sick, Nortin Hadler, MD
6. The Health Robbers, S. Barrett MD and W. Jarvis, PhD
Journals
7. Screening for Prostate Cancer, U.S. Preventive Services Task Force, October, 2011 and May 2012
8. Medical Ethics at Heart of Professionalism, Paul Ockelford, MD Medspeak, June, 2012
Magazines
9. I Want my Prostate Back, L. Stains, Men’s Health, March 2010
Newspaper
10. Prostate Surgery is Booming, but at What Cost? Sun Sentinel newspaper,
September,11, 2011
TV
11. Life After Prostate Surgery Worse than Expected, Fox News, July, 2010
12. www.pbs.org/programs/money-medicine/ featured prominently is a section onunproven screening and surgical treatment for prostate cancer.
Web
13. Prostate Cancer Surgery? Lies, lies and more damned lies, Bert Vorstman, MD
www.urologyweb.com March, 2012
About Bert Vorstman MD, MS, FAAP, FRACS, FACS
Dr. Bert Vorstman is a Board Certified Urological Surgeon with some 30 years of experience. He is Fellowship trained in Pediatric and Adult Reconstructive Urology at the Eastern Virginia Medical School in Norfolk, Virginia, a former NIH sponsored surgeon researcher and a former Urology Faculty member at the University of Miami, Florida. He also earned the honor of a Masters of Surgery Diploma through the Otago University, Dunedin, New Zealand for pioneering research on Urinary Bladder Reinnervation using nerve crossover techniques incorporating nerve grafts. This reinnervation technique could have possible application in patients with neurogenic bladders.
Dr. Vorstman is well published and has lectured nationally and internationally. He belongs to a number of organizations including the prestigious Societe Internationale d’Urologie.
Dr. Vorstman’s passion and dedication is to help men and their spouses/partners understand fully their particular prostate cancer as well as the minimally invasive treatment options available such as hifu and cryoablation for selected men with localized prostate cancer as well as radiation/proton beam options for others. In that regard he has developed a Center for Minimally Invasive Treatment Options for localized prostate cancer.
Dr. Vorstman has also developed a leading urology practice, Florida Urological Associates, pa, was instrumental in developing the Coral Springs Surgical Center, www.coralasc.com as well as developing the websites highlighting prostate cancer issues such as www.hifurx.com and www.urologyweb.com.