Patients with prostate cancer have a right to expect that their screening, diagnosis, and treatment are supported by evidence-based science. But how well does the urology community measure up when it comes to claims that standard-of-care practices are evidence-based?
Fifteen years ago, meta-researcher John Ioannidis, Ph.D., published a seminal essay — since viewed more than 3.2 million times — arguing that “most published research findings are false.” Ioannidis’s concerns are especially pertinent for clinicians who assume that their testing and treatment philosophies are inherently valid on the basis of studies designed to support these unfounded biases.
Here are five evidence-based challenges to conventional dogma in prostate cancer treatment.
1. The rapid growth of prostate cancer treatment is not driving increased survival.
The North American market for prostate cancer treatments is poised to reach USD $30.6 billion by 2025. Yet, the annual US death rate is about 30,000 and slowly decreases as each decade passes. Surprisingly, this improvement in mortality is probably not based on early detection and treatment but rather on the effect of a gradual increase in life expectancy due to better treatment of infections and comorbidities.
2. Gleason grade 3 (as in Gleason 3+3=6) is not prostate cancer.
Laurence Klotz, MD, and others have determined that the grade 3 in the Gleason 3+3 = 6 score lacks the hallmarks of cancer on the basis of its clinical outcome and molecular biology. This would mean that the Gleason grade 6 should not be diagnosed as a cancer and should not be treated or included in prostate cancer statistics.
So, which prostate cancers are potentially lethal and responsible for the 30,000 annual deaths in the United States? Essentially, those diagnosed as Gleason grades 4+3, 4+4, and anything with 5s. On the other hand, those with 3+4s and particularly those with low amounts of pattern 4 disease — the critical amount is yet to be established — seem to have a natural history similar to that of the bogus Gleason grade 6 disease described above.
More important, because of the complexity and subjectivity of the Gleason grading system, interpretation errors and incorrect diagnoses based on Gleason scores are frequent. In fact, Swedish pathologists disagreed about Gleason grades a staggering 50% of the time. A figure easily understood since the Gleason score assessment requires at least ten estimations of growth patterns seen (primary and secondary grades, 5 each). Pattern 4 disease has an additional 4 arrangements (ill-formed, fused, glomeruloid, and cribriform). Along with the percentage estimation of pattern 4 disease, there are clearly many opportunities for incorrect diagnoses.
Furthermore, prostate cancers not only exhibit different degrees of aggressiveness but also are affected by the phenomenon of field effects, which may occur through genetic or epigenetic changes. This is common in the prostate. It also explains why cancer may be detected in more than one area of the prostate or develop in another part and be of a different grade when found during surveillance at a later date.
3. PSA-based screening does not save lives.
Prostate-specific antigen (PSA)-based screening, which may also include the unreliable prostate examination, fails to save significant numbers of lives. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate cancer mortality demonstrated that “PSA-based screening results in a small or no reduction in prostate cancer-specific mortality.” Yet, despite failing to save significant numbers of lives, some 30 million PSA tests are ordered in the United States each year, conferring unnecessary risks and well-documented overtreatment.
The fact that PSA-based screening fails to save significant numbers of lives has been confirmed not only by urologists but also by others. Richard Ablin, who discovered PSA in 1970, and journalist Ronald Piana have demonstrated that PSA testing is associated with a false-positive rate of about 78%, uses an arbitrary normal range of 0-4 ng/mL, and is unable to distinguish between low- and high-risk prostate cancers because high-grade cancers often make little or no PSA. Even alternative biomarkers, including PSA derivatives, prostate cancer antigen 3, and genomic and urine tests, are not foolproof.
The transrectal, ultrasound-guided, 12-core prostate needle biopsy component of PSA-based screening randomly samples only about 0.1% of the prostate gland when comparing the total volume of the 12 core samples taken by an 18-gauge needle with the size of an average prostate gland. The grossly unscientific 0.1% hit-or-miss biopsy means that there is zero knowledge about the remaining 99.9% of prostate tissue. This test is uncomfortable (despite local anesthetic) and carries a significant risk for sepsis, rectal bleeding, erection issues, and depression. Yet, shockingly, over 1 million core-needle biopsies are ordered in the United States each year — with costly complications.
4. Prostate cancer surgery for localized prostate cancer does not improve survival.
The era of prostate cancer treatment was ushered in with a surgical approach. In 1905, H.H. Young published his modified technique, “The Early Diagnosis and Radical Cure of Carcinoma of the Prostate .” Despite the enthusiastic title, Young’s paper offered no evidence for early diagnosis of prostate cancer and zero evidence for a cure. Furthermore, Young’s conclusion that “The four cases in which the radical operation was done demonstrated its simplicity, effectiveness and the remarkably satisfactory functional results furnished” stands in very sharp contrast to his published results noting the deaths of his first two patients and prolonged hospital stays and significant urinary complications for the second two patients.
The Prostate Cancer Intervention Versus Observation Trial (PIVOT) study cast further doubt on the usefulness of surgical treatment compared with active surveillance. Published in The New England Journal of Medicine, the report concluded, “Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not substantially reduce all-cancer or prostate cancer mortality, as compared with observation, through at least 12 years of follow up. Absolute differences were less than 3 percentage points.”
Another study done by urologists , which followed patients for 29 years, implied that radical prostatectomy led to a “mean of 2.9 years of life gained.” However, the study included men with Gleason 6 disease and treated other participants with testosterone suppression, which itself can produce life extension.
Adding to the confusion, surgical studies typically included patients with a mix of Gleason grades, scores, and tumor volumes. Additionally, prostate cancer has been commonly staged on the basis of CT scans and bone scans — both highly undependable because these technologies are not sensitive enough to detect small-volume cancer spread. This particular concern has been supported by bone marrow aspiration studies and the use of sophisticated staining techniques, suggesting the presence of micrometastasis in the bone marrow of men with negative staging studies.
5. Robotic prostatectomy has never been properly evaluated for safety and efficacy.
Despite a low-level clinical study in Mexico recording no benefit for the robotic device in gallbladder and fundoplication surgery, the US Food and Drug Administration (FDA) approved the wildly expensive surgical tool in 1999 on the basis that the robotic device “demonstrated potential for future enhancements to surgery.”
As a consequence, urologists were quick to leverage the FDA’s 510(k) process to obtain FDA approval in 2001 for use of the device in robotic prostatectomy. Remarkably, this approval was achieved without any supporting studies for safety or effectiveness. Because robotic prostatectomy bypassed testing for safety and effectiveness, it’s not surprising that the list of complications associated with this surgery is alarmingly long. Sexual and bladder problems are common. Because countless men became depressed with their results following prostate cancer surgery, both preoperative and postoperative penile and bladder “rehabilitation” counseling programs were established so that men were better prepared for the surgical after-effects. A prosthetic industry took root to make implantable urinary control and penile erection devices to “cure” these tragic complications. The failure of these gadgets has resulted in even more “corrective” surgery, higher costs, and greater suffering for patients struggling to maintain relationships with their loved ones.
To What End?
The 5-year survival rate for prostate cancer is estimated to be about 100%; the 10-year survival is estimated to be about 98%; and the 15-year survival is estimated to be about 96%, regardless of the type of treatment. Despite these survival rates, the prostate cancer market continues to grow. This is even more remarkable given that 10-year survival for early-stage disease is similar whether a patient was treated or not. Yet, the quest for early detection continues unabated with the current technology du jour, the MRI-fusion study. Sadly, history has made it abundantly clear that the early-detection-to-treatment mantra for prostate cancer is not only costly, inaccurate, and risky, but it simply fails to save a significant number of men. As a community, urology’s claim about delivering evidence-based, standard-of-care medicine is in urgent need of serious review and revision.
Dedication to Anthony Horan, MD.
This article is dedicated to Anthony Horan MD, a urologist and author (The Big Scare) 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.
Written by Bert Vorstman and published in Medscape February 23, 2021
Read more.
Ablin, R., and Piana R., “The Great Prostate Hoax”.
Horan, A., “The Big Scare”.
Horan, A., “How to Avoid The Overdiagnosis and Overtreatment of Prostate Cancer”.
Horan, A., “The Rise and Fall of the Prostate Cancer Scam”.