Are We Promising More Than We Can Deliver?
By Elizabeth M. Whelan, Sc.D., M.P.H.
Posted: Thursday, October 1, 1992
ARTICLES
Publication Date: October 1, 1992
The mainstream public health community speaks confidently and smugly about how you can take control of your life and health: don't smoke; if you drink, do so in moderation; exercise; be careful of too much sun; wear your seatbelt; practice "safe sex"; and have regular cancer checkups.
In the cancer checkup department men over age 50 are urged to have regular examinations for prostate cancer including a new prostate-specific blood test, the so-called PSA. In the words of a physician writing in this magazine ("David, Why Did You Wait?" Priorities, Summer, 1991):
The PSA should be to cancer of the prostate what the PAP smear is to cancer of the uterus and cervix, and what mammography is to breast cancer. Men should be trading their PSA numbers right along with their cholesterol scores — at the office, in the spa, playing golf, wherever men gather.
It all sounded so simple, hands-on, intuitive (that's why I initially published it). Find the cancer early, cut it out, and you are home free. Since publishing that well-meaning article, I have learned that it presented only a fraction of the story and offered far reaching advice which would not necessarily deliver the promised results. Here, to set the record straight, is the disturbing truth about the detection and treatment of prostate cancer.
The Basics
The prostate is a walnut-sized gland at the base of the bladder, surrounding the urethra. It weighs only about 20 grams and is composed of gland, muscle, vascular and fibrous tissue. The prostate gland generates and secretes seminal fluid, a substance which transports the sperm at the time of ejaculation. The gland is surrounded by blood vessels and nerves which are essential for penile erection.
Despite its minuscule size, the prostate can cause great discomfort (through enlargement which is a normal occurrence with age) and can be the source of a life-threatening condition, prostate cancer. This year over 132,000 American men will be diagnosed with prostate cancer, and 34,000 will die from it, making prostate cancer the second most common cancer in men and the second most common cause of death from cancer in the United States. The number of new cases has increased in the past two decades, perhaps in part due to better detection. The death rate has also increased only slightly. This mystery disease has been personified in the media recently — Frank Zappa, the progressive rock music star, Senator Robert Dole (R-KS , Senator Alan Cranston (D-CA), Roone Arledge, president of ABC and Time Warner CEO Steven Ross are among those who have recently stepped forward to say they have this disease. Broadway producer Joseph Papp recently died from it.
How Frequent is Prostate Cancer? Who Gets It?
To understand the dilemma surrounding the detection and treatment of prostate cancer, it is essential to recognize that prostate cancer in some form is extremely common in all men, particularly as they age, but it is not life-threatening in most cases. Currently scientists estimate that eleven million American men have lesions suggestive of prostate cancer.
Among men age 90 or over who die of other causes, virtually 100 percent show signs of prostate cancer at autopsy. Among men age 40®¢49 who die in accidents or from causes other than prostate cancer, 41 percent show pre-cancerous lesions (the percentage is about 22 percent for men 30®¢39). In other words, there is a major discrepancy between the observed clinical prevalence of prostate cancer and the high prevalence of signs of the disease at autopsy. This fact is very critical in the subsequent evaluation of the alleged need for mass screening and the options for treatment.
Regarding the question of "who gets it?" genetic factors play an important role. The mortality from prostate cancer has been reported up to three times greater in relatives of patients with prostate cancer as compared to controls.
Epidemiologists have sought other possible variables to explain why some men develop clinically significant prostate cancers. Some studies suggest that very sexually active men are at higher risk — while others suggest that a low frequency of sexual activity is a factor. Occupational exposure to cadmium (in the rubber and tire industry primarily) has in the past contributed to an increased risk — but this observation is not relevant for the overwhelming majority of men today. What emerges as the most important risk factor is age. Less than one percent of patients with clinically detectable prostate cancer are younger than 50, and the incidence and mortality rises rapidly after that. The average age at diagnosis is 73 years.
Detecting Prostate Cancer: The Anguishing Dilemma
Men with early prostate cancer — presumably the stage for which a cure is most likely — are usually asymptomatic.
The "gold standard" of prostate detection has long been the digital rectal examination (DRE), hailed as "easy to perform" and "inexpensive" but, according to many, despised and rejected by most men.
On the assumption that early detection of prostate cancer would allow successful medical intervention — that is, that more men could be saved if we could detect the cancer before the tumor escapes the gland and spreads to other organs — and thus prolong life, researchers looked for new screening techniques to replace or supplement the DRE. The method that has made headlines as a "new and improved screening test for prostate cancer" is the PSA, which refers to Prostate-Specific Antigen, a test which measures a substance exclusively secreted by the prostatic epithelial cells. The immediate advantages of the PSA are that it is objective, quantifiable, acceptable to the patient and able to give a reading independent of the skill of the physician. But even the most enthusiastic PSA proponents acknowledge that is has limitations: First, a man can have prostate cancer — even advanced disease — and still have a "normal" PSA reading. Second, an enlarged — but not cancerous — prostate gland can elevate the PSA (as can, apparently, the digital exam itself, if only temporarily). But nonetheless, the "medical establishment" or at least a portion of it is now embracing the PSA as warmly as gynecologists do the Pap smear for early detection of cervical cancer. But whatever the combination of currently available prostate cancer detection tests, these undeniable and anguishing facts remain:
1. An unknown number of prostate cancers detected by any means, including the PSA, may be so-called "dormant" cancers which would never progress to life-threatening disease. PSA proponents counter that PSA will not pick up occult cancerous tumors, only those which are clinically important, but in professional circles the question definitely still remains.
2. Even with the addition of PSA to the screening scene, the following depressing statistics characterize today's diagnosis: for every 1,000 men diagnosed with prostate cancer, one-third (333) will be classified as "non-curable" because the malignancy has spread from the prostate gland into surrounding tissues; the remaining two-thirds (666) will be categorized as "curable" on the assumption that the disease is gland-limited and will be urged to undergo treatment, almost always radical prostatectomy, the removal of the prostate gland. (This is the current treatment of preference in the United States, but not in Western Europe where radiation therapy is more in vogue.)
Tragically, however, during the operation to remove the prostate in the 666 patients (or within a year or two after the operation), physicians discover that fully half of them are not curable. Instead, there is evidence during or after the operation, that the cancer has already metastasized (spread).
In other words, even with PSA in conjunction with other tests now available, it appears that two-thirds of patients who develop clinically detectable prostate cancer have already progressed to the point where a "cure" is not possible, "cure" here being defined as the complete removal of the gland to which cancer was 100 percent confined. There is nothing to be gained by removing the gland in patients who have already experienced spread of the cancer. Indeed, when such surgery does take place, it is because the cancer has been incorrectly "staged" as being "gland-limited," since, "debulking (reducing the size of) tumors that cannot be completely excised has few advocates." The questions then are posed: What is the point of screening? Who benefits from it — and who is hurt by it? Would increased use of PSA with other detection techniques find many more cancers earlier and save more lives?
Dr. Frank Hinman, Department of Urology at the University of California School of Medicine, San Francisco, writing in response to these general questions, quoted a colleague who used a barnyard analogy to shed light on the problem. Consider if you were a farmer attempting to "screen in" three species — a turtle, a bird and a rabbit, so that they would stay on your property. By the time you got the screen in place, the bird would be gone — flying over the fence to distant parts unknown. The turtle would slowly wander around aimlessly not getting far at all, and the rabbit would hop around — and might or might not jump over the fence. In other words, only the rabbit would "benefit" from the screening. The slow-moving turtle doesn't need it, and the bird will defy it.
If we apply this analogy to clinical prostate cancer, those patients with low-grade, non-aggressive, non-life-threatening prostate cancers do not need screening — or treatment. To find these "cancers" would mean anxiety, grief and probably some very undesirable consequences should treatment (surgery) be recommended. In barnyard terms, then, these cancers are "turtles," which should be left to wander aimlessly and harmlessly until the patient dies of other causes. On the other extreme, we have the "birds" — those prostate cancer patients who are, unfortunately, beyond cure because the malignancy has metastasized. These patients do not need surgery — because it will not help or cure them — but could benefit from palliative care, that is, assistance to extend their lives and make them more comfortable. To perform surgery on them would accomplish nothing in terms of cure. It would only subject them to the risk of morbidity (meaning they could become impotent or incontinent) of the surgery or other treatment.
Then we have the "rabbits" — those for whom screening might help. Referring back to our barnyard analogy, at the current time among each of each 1,000 men diagnosed with prostate cancer, 333 are "birds" at initial diagnosis, 333 are found to be "birds" within a year or two after diagnosis and treatment, and 333 have gland-limited prostate cancer — this group being comprised of both "turtles" and "rabbits," men who may never develop life-threatening disease and those who probably will move on to the life-threatening stage. If we were successful in promoting better early screening, we might shift those odds — have 333 in the "bird" category who were not "curable" because the cancer had spread — and 666 in "turtle or rabbit" phase. With early detection, the problem remains that we are unable to distinguish the "rabbits" from the "turtles" — and thus may be subjecting a great number of men to surgery which may incapacitate them without benefit.
Here we have the dilemma, and an emerging consensus (which has never quite made it to the popular press) that what we need is NOT more screening, but methods of determining which of the prostate-confined cancers are "real" and would benefit from surgery — and which should be left alone. Further, right now we need a means of determining, prior to surgery, which of the 666 initially diagnosed are really "birds," and which are "rabbits" whose lives could be saved by treatment. With all its limitations, treatment (again, almost always surgery) is not the preferred option for men who would not benefit from it and for whom the risk of death and dysfunction related to the surgical procedure is greater than the risk of the disease itself. Thus, particularly because of the high number of latent cancers, screening for prostate cancer becomes an enigma, the effectiveness of a screening program is justified only when detected cancers would surely advance to clinical significance.
Who Might Benefit from Prostate Detection Tests?
Dr. Gerald Chodak, Director of Urologic Oncology at the University of Chicago, argues that certain criteria must be satisfied to justify mass screening of men for prostate cancer. First, the means of early detection should be improved — even over what they are now with PSA. Second, survival of the screened men must show improvement over that of non-screened men. Third, there must be evidence that the death rate from prostate cancer is decreased. Given that not one of these criteria, in his opinion, has been met, Dr. Chodak argues that, "We must conclude that currently there is no scientific proof that screening is justified." The Centers for Disease Control recently agreed noting, "The value of mass screening for prostate cancer...is unclear."
Recalling the barnyard analogy of turtles, rabbits and birds, others have raised questions about the value of screening by raising a question (known in the medical literature as "Whitmore's question," after Dr. W. F. Whitmore, Jr. ,the recently retired head of the Department of Urology at Sloan-Kettering Cancer Center in New York). Considering the poor therapeutic results of advanced disease (birds) and the favorable natural course of early states of disease (turtles), "Is cure possible in those for whom it is necessary, and is cure necessary in those for whom it is possible?" In other words, can we really cure men whose prostate cancer has "flown away" — the "birds"? The answer tragically is no. To treat these men with surgery not only would fail to cure them, but would, as Dr. Hinman points out, "set up a sequence of diagnostic steps and treatment programs that might seriously interfere with the quality of life" Furthermore, do we really need to treat those who we can potentially cure — the "turtles" — who might die at eighty of something totally unrelated to prostate cancer? The answer is clearly no. What is not clear is how to separate the "turtles" from the "rabbits."
Who Is and Is Not Recommending Screening?
The great debate about massive screening for prostate cancer, including use of the PSA, centers on two concerns: the potential for finding tumors that are not life-threatening and the potential for finding tumors that are not treatable. As one physician puts it, "There are small gains for a few at the expense of many." Looking back at the 1,000 men under today's diagnostic schemes, then, to save the lives of a maximum of 333 of them (probably somewhat less, because an unknown portion are likely "turtles" who will not progress to life-threatening disease), you are potentially causing some degree of incapacitation without benefit in 666 others.
Pro-Screening:
Unshaken by the controversy, there are some — most notably Dr. William J. Catalona, a researcher at the Washington University in St. Louis — who remain enthusiastic about mass screening with PSA, supplemented by other techniques: "It is very conceivable," he writes, "that using (these techniques) the statistics in prostate cancer could be dramatically altered. Instead of 7 out of 10 cancers being advanced at the time of diagnosis we could flip that and 7 out of 10 could be in the early stage." Agreeing with Dr. Catalona are researchers such as Dr. Ruben F. Gittes of the Scripps clinic in La Jolla, California who states unequivocally, "I think it is just as important as having a cholesterol test."
Some physicians are still adamant about the desirability of prostate testing even though they admit its effectiveness has never been proven. Dr. Patrick Walsh from Johns Hopkins Hospital argues that there is indeed no proof that screening saves lives. He writes that, "This issue has never been studied and no one has ever shown that an early diagnosis of prostate cancer does not prolong survival."(An argument that the test is innocent until proven guilty.) But advocates of PSA screening haven't addressed the problem that massive testing will give us results which we may not be equipped to interpret accurately.
Screening and Skeptics
Among the many screening skeptics — and PSA skeptics specifically — are Dr. Michael P. O'Leary of the New England Medical Center in Boston who says, "PSA is a useful tool in following patients with known prostate cancer, but is still not a useful tool for screening. It is not sensitive or specific enough." Dr. William Fair, Chief of Urology at Memorial Sloan-Kettering Center in New York City, is even more skeptical. Dr. Fair writes that, "PSA could also stand for 'priority seems awry.' We don't have any evidence that early detection leads to increased survival [and] we don't have the faintest clue of how to distinguish indolent from more aggressive prostate cancers."(emphasis added) Once again Fair raises the concern of patients suffering from treatment without benefit. He also questions the cost and priority in our spending on widespread screening: "Even if Medicare would offer reimbursement . . . the test [PSA] cost is prohibitive." (The test can cost $85 or more.) Screening 28 million American men over 50 could cost $2.4 billion which Fair notes is "$400 million more than the National Cancer Institute's entire budget."
"But shouldn't we screen just in case?" Those who favor this approach, critics say, ignore the potential harm screening could do (diagnosing cancers that would never shorten lives and causing death, disability and suffering associated with treatment). There is a one to two percent death rate associated with prostatectomy, not to mention the incontinence and impotence that can result. If 30 percent of the 25 million screened men over 50 had cancer detected and subsequently excised in surgery, the expected one percent mortality would cause 75,000 deaths, 41,000 more than prostate cancer itself. As Dr. Hinman concludes, "The cumulative harmful effects of screening many men may outweigh the benefits of earlier diagnosis of a few."
Should You Undergo Annual Prostate Screening?
There are two different perspectives from which to evaluate the decision about whether to screen. From a societal point of view, it seems clear that recommendations for mass screening are not justified. The resources which would be invested in mass screening might be better spent elsewhere toward the goal of reducing deaths from prostate cancer.
However, from the individual view there may be some other considerations, including a family history of life-threatening prostate cancer. For these individuals regular screening may indeed provide the benefits of early detection of what are likely aggressive and life-threatening cancers. Age at screening is yet another factor which may be considered for an individual's decision. Some physicians argue that tests before age 50 are not necessary or cost effective because the frequency of clinically detectable cancers is so low and that tests after age 70 are not as necessary because any cancer is less likely to be life-threatening. While the overwhelming majority of urologists I consulted agree that screening for prostate cancer has never been shown to prolong life and that there are serious risks in diagnosis and misdiagnosis, none would directly say to men "don't bother to be screened." This apparent contradiction perhaps can be explained in light of legal liability and the instinctive, closely-held belief, despite the lack of data, that early detection through screening is beneficial.
The National Cancer Institute, for example, still recommends that a rectal exam "be part of a regular checkup for all men over 40." The NCI does not recommend PSA for diagnosis calling it "useful in monitoring a patient's treatment, but... not specific enough to be used alone to detect prostate cancer."
Prostate Cancer: What Should the Priorities Be?
While it is impossible at this point to make specific recommendations for individuals or even large populations on the desirability of screening or the "correct" option for dealing with what appears to be a gland-defined prostate cancer, a review of the current literature leads to these conclusions about priorities.
Money being spent on mass screening for prostate cancer might be spent in better ways such as:
1. Looking for a means to distinguish latent "turtle" prostate cancers from potentially life-threatening curable ones "rabbits." Were this technology available, 333 of the 1,000 men currently thought to be curable could be analyzed to separate out those whose cancer was not life-threatening from those who were at risk of an aggressive and lethal cancer. With this technology in hand, massive screening would make more sense in that the growing proportion of men diagnosed with gland-limited cancer could be assured with medical authority that treatment would indeed save their lives. If we had the ability to "stage" properly prostate cancer and we could limit surgery to those who would clearly benefit from it — that is, men whose cancer was confined to the gland and in whom it was determined that the malignancy would almost definitely spread and become a cause of premature death — then those arguing for massive screening would have a far stronger case. Early diagnosis through screening would then benefit the small portion of men who need it, namely those men with curable, life-threatening disease. The bottom line is, as Dr. Hinman writes, "The great need at present isnot to find more cancers, but to be able to detect those which are harmful and curable."
2. Looking for non-surgical, non-maiming means of dealing with prostate cancer.
3. Learning why some men (black Americans) are at such higher risk — so that we might initiate successful intervention programs to prevent the disease in the first place.
4. Testing promising new pharmaceuticals which might prevent clinical onset of prostate cancer in high-risk men.
But instead, we find ourselves in desperately trying to find cancers early — with techniques that raise more questions than answers, prompt us to attempt to "cure" cancers that don't need it and "treat" cancers that are defiant of cures.
This is an excerpt from an article published by Across the Board in October, 1992. For the full article contact ACSH.
Roger's Story
Roger, a 56-year-old insurance executive, was 54 when first diagnosed with prostate cancer. He underwent radical prostatectomy soon after diagnosis. Two years later his PSA reading was again elevated, and he underwent radiation therapy:
I had never felt sick a day of my life and one day just over two years ago, I went in feeling fine for my annual physical, and I came out half a man.
The year before, my internist had noticed a little nodule on my prostate and ordered a biopsy (under general anesthesia) which took little bits from all over the gland for microscopic inspection — and it came up negative. I forgot about the whole thing and thought that was that. But a year later, that nodule was still there. The urologist did a PSA and a sonogram of the suspicious area while simultaneously taking a biopsy. This time it turned out to be positive along with a high PSA (15 or 16 — and that's pretty high). He immediately recommended surgery.
I shopped around for other advice — four different doctors (although in retrospect I probably should have gotten more variety of opinion, as all four were surgeons from the same hospital). They said the same thing: you are too young not to take immediate action, and that meant removal of the prostate gland.
I was in the hospital for two weeks, and it was hardly "routine" because I developed a blood clot that could have been life-threatening. They put me on a blood-thinner for months after the operation, but at least I thought this nightmare was over. The word from the doctors was that assuming there was no other sign of cancer, and the tumor was limited to the gland, I was home free. I could put it in a little jar on the mantle, and I would be golden. I sincerely believed that after the radical surgery I was out of the woods.
But two years later, during another routine physical my internist noted — casually — that my PSA was up to 15 again. He didn't seem upset so initially I was not. But that night I saw Senator (Robert) Dole on television discussing the fact that he has an elevated PSA of four, and I was alarmed for myself; and also puzzled, wondering why I had a PSA reading at all when I had no prostate gland.
I found myself right back in the medical maze, with bone and CAT scans and an eventual diagnosis that "maybe" there were some lurking cancer cells in what they call the "prostate bed." I was told that cobalt radiation was the answer to kill the cancer cells.
Again, as two years before, I was feeling fine — no symptoms. The radiation was to kill the cancer cells that might be there. What choice did I have? The psychological as well as physical symptoms of that treatment were overwhelming for me — and now I am playing the waiting game again, waiting three months to get another PSA reading. Waiting for some magic number that will determine the rest of my life.
My advice to men who are diagnosed: take control of your life and your fate, become informed. I knew nothing about prostate cancer before my diagnosis. I am now something of an expert. Insist that your doctors be up front with you about the proposed treatment — and the side effects. I was told that I faced a 50/50 chance of impotence and incontinence. The potential loss of sexual ability was an extremely important issue to me. My wife and I pressed this point with my doctors, many of whom seemed annoyed by my questions and perplexed that sex was important to me when they were stating that my life was in danger. "I'm going to save your life, Roger," one physician said; "I do not want to talk about the other ancillary matters." But for me these 'ancillary matters' were just as important as prostate cancer. In fact, I might not want to live if I were sexually incapacitated.
One surgeon thought he had the answer to calm my concerns: he recommended I interview a patient on whom he has just performed a prostatectomy. I did so — only to learn from this 65-year-old man that he had no concerns whatever about sexual dysfunction because he and his wife had "given that up" years ago and now he just wanted to "live long enough to play some good golf." Well, that was certainly not my view of life, and I would have been appreciative if the physicians counseling us understood the importance of quality of life as well as extending the years of life. (The 65-year-old man later asked our mutual doctor why he had sent a 'sex maniac' to interview him).
Physicians seem to want to put a pretty face on everything — withholding important information, preferring to give you bad news a little bit at a time. I would have preferred it all up front. If I had known the full implications of the temporary incontinence I faced, I would have dealt with it much more effectively — but I was not informed.
I understand I cannot ask for guarantees or assurances from these doctors — but what I do not understand is why there are not more hard data on the outcomes of surgery, radiation and the like. The doctors I interviewed must have records of hundreds of patients. What happened to them over the course of 10 years? Were they all like me, radical prostatectomy then back for radiation and who knows what else two years later? Or am I just an unusual case? No one would give me answers. I am shocked at the dearth of real statistics here.
Am I in favor of screening? I'll give you a tentative yes on that because I believe it may have saved my life. I tell everyone who will listen to get checked, find it early. But did screening help me? I do not know and can only hope the answer is yes. So I eat lots of beta-carotene-rich foods — broccoli, carrots and mangoes for breakfast — just in case it will help. I figure I should try anything that might tip the scales even a bit in my favor.
(From Priorities Vol. 4, No. 4, 1992)
