Poor science underlies the USPSTF recommendation about PSA-based screening


Whatever we may think individually about the recent decision by the U.S. Preventive Services Task Force to recommend against the use of PSA testing as a means of “screening” for risk of prostate cancer, we would be wise to understand that at the heart of this decision is poor science. And that poor science is not poor interpretation of the data available to the task force, it is poor science in the design and conduct of almost every trial carried out with the intent to demonstrate or not demonstrate  that PSA-based screening actually either saves lives or improves quality of life of men with prostate cancer.

From the very beginning of attempts to validate the idea that the PSA test might be able to help us know whether early diagnosis would properly lead to early treatment of appropriate patients, there have been inbuilt personal and structural biases that have led to poor clinical trial design and poor clinical trial execution. And this is not some sort of important “new” finding that has been unknown to all those involved.

The initial studies designed to investigate the possibility that we could use the PSA test to screen men of more than 50 years of age for prostate cancer were funded by industry and led by a physician who was already convinced that the answer was “yes.” The data from the study reported by Catalona et al. in the New England Journal of Medicine in 1991 showed something that no one argues with … that if you use a PSA test as well as a DRE and ultrasonography you can increase the likelihood of being able to find men who have pathologically identifiable cancer in their prostates. This is not — and never has been — the critical issue. The issue is whether that finding is clinically meaningful, and if so for which patients.

The data review by Chou et al., which acts as the basis for the recommendation now proposed by the USPSTF, provides a thorough assessment of every significant study that has attempted to demonstrate that screening for prostate cancer with a PSA test (with or without a DRE) is associated with either a prostate cancer-specific or an overall survival benefit. Not one of those studies has ever demonstrated an overall survival benefit. Furthermore, the data provided by the authors in Table 1 of that paper clearly demonstate that not one of the six large studies meets the standards for good evidence-based medicine. This does not, however, mean that they do not provide compelling evidence to “believers” in the value of PSA screening. At least two of them do (the Gõteborg study and the ERSPC study) — but each of these studies was still badly flawed from the point of view of design and implementation.

If these data were ever used in an attempt to have to PSA test approved by the US Food & Drug Administration (FDA) for extending the prostate cancer-specific or overall survival of men with prostate cancer, they would not come close to meeting the necessary standard. But the FDA has never been asked this question. The PSA test was approved by the FDA many years ago for “the measurement of serum PSA in conjunction with digital rectal examination (DRE) as an aid in the detection of prostate cancer in men aged 50 years or older.” And that is exactly what it does. It does not and can not help us to know whether a man needs to be treated unless the PSA level is strongly suggestive of locally advanced or advanced disease.

It has long been unclear to the present writer why the urologic oncology community has been so unwilling for so long to conduct a single, large, randomized study to define — according to the standards of evidence-based medicine — whether PSA testing could, in fact, be proven to extend survival of men diagnosed with prostate cancer. It seems highly likely that if a really well-designed study similar to the Göteborg study — but with improvements — had been initiated in the USA back in the early 1990s (with men carefully stratified by age, by risk factors, etc., with centralized pathology, and with a large enough pool of control patients so that anyone who actually got a PSA test in the control group could have been eliminated from the data set), we would probably know by now — with absolute certainty — that yes, PSA screening could indeed extend the lives of a subset of men diagnosed with at least high-risk prostate cancer at between 50 and  70 years of age. And it may well be that this is the only subset of men in whom we could ever prove such an effect, because the number of men diagnosed with intermediate- and high-risk prostate cancer in their 40s is so small. We have lost the chance to do this study now, and we have lost it because the clinicians who were involved in the early use of the PSA test to screen for prostate cancer were already convinced that the test was compellingly wonderful.

Readers need to understand that the USPSTF is making its recommendation based on the available, prospective, high quality, clinical data required by the fundamental guidelines of evidence-based medicine. They have probably come to a poor decision from the point of view of clinical need. But the fundamental reason for their decision comes back to poor science. The urologic oncology community failed to design and conduct studies that met the highest standards of evidence-based medicine. Many of us who have been around for a while understood just how flawed those studies were from the time they were initiated.

It is easy to pick on the USPSTF if one does not understand exactly what they are charged with doing. They are asked to assess data that meets formal standards for evidence-based medicine and then make a recommendation about whether a particular test  or other initiative actually meets those standards in prevention of a specific disorder. We may not like their recommendation. We may not agree with their recommendation. Society may not even have to abide by their recommendation — and it didn’t in the case of the mammography recommendation issued by the USPSTF a while back.

Eliminating access to the PSA test today would be a disaster, but this recommendation from the USPSTF may be a good thing even if it doesn’t get implemented. It may help men and their doctors to think harder about the impications of what they are really doing. It may help to stop thousands of men every year who have an elevation in their PSA at age 75 to not have a biopsy that they don’t really need. It may help thousands of men every year who have a diagnosis of low-risk prostate cance between the ages of 50 and 75 years to decide that active surveillance is wiser than immediate surgery. And it may help thousands of men in their late 70s or 80s to decide that at their age PSA testing is a complete waste of their time because their chances of a prostate cancer-specific death are already near to negligible.

We need to move on. Our focus should be on finding a test that really can discriminate between men who have clinically significant prostate cancer and those who don’t … and when we think we have found such a test, we would be wise to conduct trials that actually prove that it can lead to an overall survival benefit in highly defined groups of men.

29 Responses

  1. People generally agree with facts if they give them the answer they want.

  2. Mike,

    Your post could not have been written any better. You have correctly stated what USPSTF has said; that the harms of testing and treating a large group of men appear to outweigh the benefits, and the benefits are very small at best. However, their statement does not say men should not be tested. Rather, their message really is don’t tell all men that testing is the best thing to do; stop misrepresenting things to the public.

    Those who are outraged by this report should consider the following:

    — Cancer of the stomach, kidney, and pancreas kill about 60,000 people per year.
    — CT scans would likely identify many of them before they cause symptoms when they are easier to treat, but the public is not being advised to get screened for those diseases.
    — Why isn’t there a similar outrage about not screening for those diseases? Is it because the CT scan is more involved than a simple blood test, or that we have no proof it would save lives, or the possibility that it might cause more harm than good?
    — How many drugs have not been approved because, when properly tested, they failed to show that the benefits outweigh the harms even though some people were likely helped?

    As you state so well, more consideration should go into deciding who should be tested and treated and the public should stop receiving advice not supported by good science.

  3. Gerry:

    My concern at this time is that the very way the USPSFT recommendation is actually phrased may be implying something rather different than what you suggest. According to a New York Times article today, several health insurance companies are already looking at whether they should be covering the costs of PSA testing.

    If what the USPSTF is saying is, “There is no evidence to support mass, population-based PSA screening for risk of prostate cancer, but the use of this test may be appropriate in selected, healthy individuals after discussion with their physicians,” then it would help if they were to say that.

  4. I think nobody disputes the need for a wonderful, precise test for prostate cancer and for a great treatment. But, alas, the only easy test available today is PSA, so let’s not through out the baby with the bath water.

    Even the writer of this blog admits that the results of a well conducted study — the Goteborg study — are conclusive and demonstrate that PSA testing saves a lot of lives of men that are between 50 and 70.

    So the real conclusion is that the benefit of PSA testing is marginal if your age is higher than 70. But that is not what the USPSTF recommendation says. It says PSA screening is not effective and does not contribute to reducing prostate cancer mortality. The ensuing discussion raises men concerns by raising the specter of incontinence and ED. This without taking into account the way different first-line treatments affect the patient, the fact that incontinence is in most cases a short term effect (1 to 2 months) and resolves itself after that. The discussion also doesn’t touch a deeply problematic psychological issue related to ED. I think most men will agree that the psychological impact of ED is different for a 50-year-old and a 75-year-old. Honestly, there is a difference how important a man’s sex life is whether he is 45 or 75. I am not aware of any study researching the impact of ED on men at different ages, but such a psychological study may be helpful to our discussion.

    In conclusion, we can fairly say that PSA screening is essential at the earlier age — between 50 and 70 when prostate cancer can be diagnosed when still contained, allowing nerve sparing. Without PSA testing we will not be able to proceed with a diagnose using more advanced tools such as ultrasound and biopsy and we will not be able to make an intelligent decision regarding our health, be it active surveillance, prostatectomy, radiation, hormone therapy or whatever science brings forth.

    Most people don’t read or are unable to follow the fine points of statistics and the only retained information is the headlines, which will stay as “PSA screening is not recommended.”

    It seems to me that USPSTF has done men great damage and is set to roll back much of the progress made in the diagnosis of prostate cancer.

    Men like Dr. Brawley should be chastised and have no place in an organization like the ACS. I suggest the prostate cancer patient community initiates a petition calling on the ACS to fire Dr. Brawley and find a candidate for the Chief Medical Officer position who is more supportive of the case of the 240,000 men who are detected with Pprostate cancer in this country every year.

  5. There is an analogy (admittedly imperfect) between PSA as a screening test for prostate cancer and neck ultrasound as a screening test for thyroid cancer. Increased use of the latter has likely increased the number of biopsies of nodules and of subsequent thyroidectomies. However, the process is not as simple as ABC. There are authoritative criteria for proceeding from one step to the next, such as hyperfunction (which all but rules out cancer), nodule size, and growth rate. Analogously, I think that the question with PSA is what the best algorithms are for its use, involving such matters as rate of rise, percent free PSA, and risk factors. I expect that PSA screening that followed a good algorithm would show a clear benefit.

    The question in my opinion is not whether to use the PSA but how.

  6. Dear Reuven:

    (1) Once again, I did not state any of the things you are suggesting I stated.
    (2) The Goteborg study did not demonstrate an overall survival benefit for men who were screened compared to the men who were not screened, and while it was better conducted than any other to date, it still had flaws.
    (3) You are correct in stating that the USPSTF is recommending that mass, population-based screening for risk of prostate cancer based on the PSA test is not a valid method of managing prostate cancer risk, and I agree with that recommendation (as I have for a very long time).
    (4) However, this does not necessarily imply that risk-based testing of individuals is inappropriate.
    (5) It is not the fault of ther USPSTF that the public and the media do not understand the criteria by which the USPSTF make their recommendations.
    (6) The conclusions you draw above are based on your personal interpretation of the available data, not the criteria by which the USPSTF is asked to assess the same data.

  7. Herb:

    I would go one step further and say … The question is not whether to use the PSA test but how and in whom.

  8. This information from urologist William Catalona should have been provided the USPSTF, as well as the following from medical oncologist Stephen Strum:

    “Dear Patients & Colleagues,

    “Hoping to avert 200 more emails about how I feel re PSA screening (as if everyone that knows me does not know this already), I am pasting in my response to the New York Times below:

    “The problem we face in healthcare today is the age old “don’t confuse the message with the messenger”. I am a medical oncologist involved in cancer diagnosis and treatment for > 40 years and with total focus on PC (prostate cancer) since 1983. I would say, without hesitation, that the PSA is the best biologic marker for one of the most common malignancies that mankind faces. That said, there are caveats that involve the MESSAGE and the MESSENGER: (1) Understand the strengths and weaknesses of PSA testing, since there are quite a few; (2) realize that the TREND or change over time is far more significant than one test result; (3) understand factors that can raise or alter the PSA test results, e.g., ejaculation within 48 hours of the test, prostatitis, urinary tract infection, different labs using different methodology, time of the day the test is taken.

    “Then couple the above understanding with MESSENGER factors. Many physicians place the business of medicine before medical business. The available RISK ASSESSMENTS for the individual patient are almost never done (these involve tools called nomograms and artificial neural nets) and the MDs evaluating the patient are often flagrantly biased towards an invasive procedure involving their particular speciality. True multi-disciplinary panels are seldom found.

    “Therefore, the issue or the “blame” is not the PSA test, which is indeed of huge value; the issue is what we do with this gift; do we use it or abuse it. Perhaps, if we can’t learn how to use the PSA properly, the panel decision recently reached is appropriate. For me, in my practice of PC, the introduction of the PSA has meant the world of difference to thousands of patients under my guidance. I would welcome the challenge to be presented with any patient scenario relating to PSA testing and objectively present my findings.

    “Men at some time are masters of their fates:
    The fault, dear Brutus, is not in our stars,
    But in ourselves, that we are underlings.

    “Stephen B. Strum, MD, FACP
    “Ashland, Oregon”

  9. Dear Chuck:

    I feel I need to tell you that I found Dr. Catalona’s lecture at the AUA this year to be outrageous. It is statistical nonsense. Just a couple on months before he gave that lecture he was claiming that he would be telling the audience that PSA testing saved 22,000 lives a year in America. By the time he actually gave the lecture he had managed to increase this to 33,000 lives a year. I have yet to meet a statistician who can justify either of these claims.

  10. Dear Mike:

    I greatly appreciate your great work and knowledge, but I am afraid there must be some misunderstandings between us and I would like to make things clear, for the benefit of all men who may be concerned about PSA screening and its merits.

    (1) I am not sure what are the things I stated wrongly. I think I only quoted from your post. “… yes, PSA screening could indeed extend the lives of a subset of men diagnosed with at least high-risk prostate cancer at between 50 and 70 years of age. …” I am not aware of putting other things in your mouth and if I did, I apologize.

    (2) I am not aware of any flaws in the way the Goteborg study was conducted. Since it was published in Lancet, I assumed it was rigorously reviewed and approved. I would greatly appreciate it if you could educate me regarding the study’s flaws, since I quote him extensively. It would be great if you could include references to professional criticism by statisticians or epidemiologists who analyzed the study and found flaws in it.

    Meanwhile, I read the study again. According to its authors’ conclusions, “The rate ratio for death from prostate cancer was 0.56 (95% CI 0.39–0.82; p = 0.002) in the screening compared with the control group.” It seems to me that an almost 50% reduction in death rate is a good enough result that justifies PSA screening.

    Furthermore, reading the detailed data, one finds more interesting facts:

    (a) The number of men needed to be screened (NNS) to prevent one death from prostate cancer was 1,410 (or 1,068 in men who were actually screened), which is similar to breast and colorectal cancer screening.
    (b) Most of the prostate cancers diagnosed in the screening group were early-stage disease. The number of men with advanced prostate cancer (metastases or PSA > 100 ng/ml at diagnosis) was lower in the screening group than in the control group (46 men vs 87; p = 0.0003)
    (c) An analysis of the rate of prostate cancer deaths (Table 4 in the study) shows a very significant decline in prostate cancer deaths for the screened group compared to the control group, in particular for the younger age cohorts. Thus, in the 50-54 age group, the death rate in the screened group is only 32% of the death rate in the control group. In the 55-59 age group the ratio is 22.4% only.

    I have read numerous times the statement that “PSA screening is not a valid method of managing prostate cancer” and at the same time that “this does not necessarily imply that risk-based testing of individuals is inappropriate.” I still don’t understand that. If PSA is not a valid method, than what is the valid method? I would be much more receptive to criticism of PSA testing if it came with a clear statement of what the 240,000 men detected this year should do.

    How would one decide he is at risk absent a previous family history. (I apologize for introducing personal anecdotical data, but I am the first in my family to have been diagnosed with prostate cancer.)

    I strongly disagree with the free pass given to the USPSTF. It is not an obscure scientific board. It is a governmental board that is supposed to educate and help the public and they should be very strongly aware of how the information they publish influences the decisions of laymen.

    I assume they do understand how the public will read this press release and the fact that it will cause people to oppose PSA testing.

    We cannot relieve them from this responsibility.

  11. Reuven:

    In your prior post you wrote, “Even the writer of this blog admits that the results of a well conducted study — the Goteborg study — are conclusive and demonstrate that PSA testing saves a lot of lives of men that are between 50 and 70.” That is not what I had said at all. I had very carefully written that:

    “if a really well-designed study similar to the Göteborg study — but with improvements — had been initiated in the USA back in the early 1990s … we would probably know by now — with absolute certainty — that yes, PSA screening could indeed extend the lives of a subset of men diagnosed with at least high-risk prostate cancer at between 50 and 70 years of age.” [Bold italic added for emphasis.]

    That is not a statement that the Goteborg study proved this concept. It didn’t. The Goteborg did, indeed, show a significant benefit in terms of prostate cancer-specific survival at 14 years. However, it showed no benefit whatsoever in terms of overall survival. Actually the overall survival of the men in the screening arm of the Goteborg study was worse that that of the control arm. I have still not been able to resolve that. The methodological problems with this study are listed in Table 1 of the paper by Chen et al. (And Chen et al. were not members of the USPSTF.) Just because something gets published in The Lancet or the New England Journal of Medicine does not mean it is some sort of perfect study. The Goteborg study is the best we have. It followed men for 14 years. It had fewer methodological flaws than the ERSPC or the PCLO trial but it still had flaws. The patients were iregularly tested; the PSA screening value changed over time; the authors claim that only 3% of the control group received PSA tests — but there is no explanation of how this was calculated.

    There are now extensive data from Vickers, Lilja and others suggesting that a man with a PSA test result of less than about 0.7 ng/ml at about the age of 40 is at low risk for clinically significant prostate cancer, whereas a man with a PSA test of > 0.7 is at higher risk for clinically significant disease over the next 25 to 30 years. This information, combined with family history and ethnicity, potentially offers a methodology for risk-based PSA testing over time (as explained several times on this site in the past 3 years). This hypothesis needs to be rigorously tested.

    The advocates for mass screening constantly neglect the fact that 83% of men are at absolutely no risk for clinically significant prostate cancer in their lifetime … even though we know that by the time they get to 60 years of age there is a pobability of 50-55% that prostate cancer tissue would be found in their prostates at autopsy. That probability continues to rise as they get older. By the time a man reaches 75 years of age, he has a 70% probability of cancer in his prostate … but his risk of prostate cancer-specific mortality is already declining.

    In the past 20 years we have massively increased the numbers of men who get diagnosed with prostate cancer. We have, most certainly, reduced the actual postate cancer-specific mortality rate, when expressed in age adjusted terms, by about 40% from 1992 to 2007, but it is not clear exactly why. PSA testing is undoubtedly a significant component of this, but we know it can’t be PSA “screening” because most men don’t actually get “screened” … they get a very occasional test.

    The USPSTF does not, in fact, have any obligation to “educate and help the public.” The USPSTF makes a recommendation to the Agency for Healthcare Research and Quality (AHRQ), which is then responsible for forwarding that recommendation to others and acting on it itself. AHRQ most certainly does have an obligation to educate and help the public. They have been telling people about the inherent risks associated with PSA testing for several years — rather well in my opinion. But that doesn’t mean that it has been effective as education.

    Last but not least, I am not giving the USPSTF a “free pass.” I would like the USPSTF to be asked to explain how their recommendation should be implemented in the real world by doctors who have clinical responsibilities to their patients. Dr. Chodak has expressed the opinion, from his perspective as a community-based urologist, that the USPSTF recommendation is only that men should not be told that everyone should get a PSA test. I am not sure this is that simple.

    As Bill Manning noted in the first comment on this article, “People generally agree with facts if they give them the answer they want.” He is correct. The USPSTF is stating “facts” that the survivor community doesn’t want to hear. I have been stating the same “facts” for the best part of 20 years (albeit with a vastly less significant evidence base early on). The USPSTF stated similar “facts” about breast cancer screening. Komen for the Cure and others disn’t want to hear those “facts” either, despite the “fact” that many eminent members of the breast cancer community actually agreed with them. We have deluded ourselves about the value of the PSA test for the best part of 20 years. Can it help us to identify men at risk for having prostate cancer cells in their prostates? Absolutely it can. Can it help us to identify men at risk for clinically significant prostate cancer and change their life expectancy? That has never been demonstrated.

    Last but not least, my suspicion is that the USPSTF recommendation is going to change few minds. The survivor community will continue to believe that everyone should get regular PSA tests starting at age 40 or younger. The academic epidemiology community (along with a few idiots like me) will continue to point out that there are no category 1, evidence-based data that can be used to justify mass screening. A subset of men will get annual medical exams, and the sensible ones among them will actually have a conversation with their doctors about the pros and cons of PSA testing. The majority of men will still continue to avoid going to see a doctor until they have symptoms of some disorder that forces them to take action.

    Until we have a better set of tests, as I have said a thousand times before, we are never going to resolve this discussion for one simple reason … most of the survivor community and a large percentage of the urology community are not willing to acknowledge the truth … which is that all a PSA test does is tell you whether you might or might not benefit from a biopsy, but it can’t tell you that with any degree of accuracy, and even after you have had the biopsy — for most men — the question of “now what” is almost impossible to answer with accuracy either.

    The PSA test is a useful test, and it is certainly the best test we currently have … but we don’t use it very well and we also have a tendency to use it in the wrong people at the wrong time without giving them any un derstanding of the risk/benefit ratio,.

  12. I’d still like to learn how the USPSTF proposes we diagnose intermediate- and high-risk prostate cancer in asymptomatic men between the ages of 40-70 without mass screening using the PSA with or without a DRE. The task force ignores this population most likely to die from the disease if diagnosed once symptomatic.

    Periodic mass screening will pick up many of the men with greatest risk. Recognizing that the PSA test in and of itself is not harmful and provides information not treatment, the focus should be on better processing that information. A friend this evening said to me he cannot understand why the PSA test in and of itself is harmful — I explained it is not and that the task force confuses information with treatment.

    As a back-up position, men with a family history of hormonal cancer, of African-American heritage, or exhibiting a baseline PSA in their early 40s of > 0.7 should still be screened periodically.

    RD

  13. Rick:

    I would like to know that too … but to be fair to the USPSTF that was not the question they were aked to address.

  14. What all of this leaves me wondering is, okay, what if my doctor hadn’t been monitoring my PSA? How might my prostate cancer adventure have played itself out differently than it has? The first symptom I had was difficulty urinating, but Flomax took care of that at least for a while. By the time we did do a PSA-suggested biopsy, my prostate was saturated with cancer, and it had already spread throughout my body. What if we hadn’t discovered that until 6 months or a year later? How might that have changed my prognosis? As it is, we radiated my entire pelvic area, eliminating any possible involvement of the bladder or colon. And since then it has only been in my bones.

    That was all in early 2006. Five and a half years later I’m still chugging along. … Would that be the case if we’d caught it later when its symptoms/side effects forced our hand? Maybe. … In truth, being treated has been no bed of roses. But in catching it as early as we did, we were able to nip it back numerous times before it became a real problem, and even now leave me with a reasonably good quality of life. In the meantime, dozens of acquaintances have been diagnosed with and have succumbed to other kinds of cancer. I have a 25-year-old son, and there is no way he isn’t going to have his PSA regularly monitored. To be at risk, and to choose ignorance over knowing seems like only something that people who don’t feel they are at risk would ever think of recommending.

  15. John:

    The very fact that you had urinary tract symptoms leading to treatment with Flomax means that you do not fall into the group of men being discussed by the USPSTF. They are discussing “healthy,” symptomless men. On the basis of the USPSTF recommendation nothing would have changed in your case. (Of course some people would suggest that you should have had a biopsy at the time of your original urinary tract symptoms to rule prostate cancer out as a cause of those symptoms.)

  16. Mike — You raise a good point … What WAS their original charge?

    IF it was to asses the effectiveness of the PSA test as a mass screening instrument, I would suggest that they should have considered the interests of men with intermediate and advanced disease. This could have been done by carving out an exception as they did for symptomatic men (my back-up position above), or, they could have discussed screening all men to find this sub-group — then have discussed the cost-benefit of saving these lives.

    Either way — don’t blame the PSA test; blame the way we use the information derived from the test!

  17. Rick:

    Read the full text of the actual recommendation. Most people are just reading the “headline.” And see the next post on how the USPSTF thinks the recommendation should be implemented.

  18. As an interested party (I’m a prostate cancer survivor) with some background in statistics. (I’m an economist.) I think there are some statistical problems with relying too much on the fact that the European studies do not find that the PSA test significantly reduces overall mortality.

    The question is, what is the null hypothesis? And what is the structural model being used of what determines mortality?

    If the PSA test is found to reduce prostate cancer mortality, we need to then model possible negative side effects on other types of mortality. Obviously there can be immediate mortality related to surgery. But I don’t think that in the European study the immediate mortality related to surgery can possibly explain the discrepancy between the prostate cancer-specific mortality and overall mortality.

    Statistically, there will be a higher ratio of noise to signal in the overall mortality rate that will make it more difficult to detect effects of PSA testing on overall mortality.

    I have not seen a statistical test of whether the overall mortality results can statistically reject a different null hypothesis: that overall mortality is reduced by the reduction in PSA specific mortality adjusted for immediate surgical mortality.

  19. Let me first say, I have not re-read the ERSPC study.

    As I recall it found a 30% reduction in the prostate cancer-specific mortality rate — significant I would say. Originally it was indicated at 20%, still significant, but corrected to 30% about 6 months after publication.

    As Mike has pointed out, there were design flaws with the study, and from memory the statistical reliability of the results were poor. I guess the USPSTF must be discounting the study on the basis of its poor statistical reliability.

    RD

  20. Dear Ralph and Rick:

    The original authors of the ERSPC study long ago stated that the data from their study was insufficient to justify mass, population-based, screening for prostate cancer. I would guess that the USPSTF would consider that they could take the original investigators word for that … but the article by Chou et al. in Annals of Internal Medicine explains exactly what their review, conducted at the request of the USPSTF, considered to be the findings and flaws of the ERSPC study.

  21. Mike,

    I think the discussion about PSA screening should be part of a broader discussion on screening in general. As far as I understand, there are no tests that are 100% sensitive or specific. We carry out tests that provide some indication of risks and based on the results people get treated with drugs, surgery, diets, etc. This is true for different kinds of cancer as well as for heart diseases, diabetics, etc. However, we don’t hear about any objections to testing for cholesterol or glucose. It is true that anti-cholesterol treatment is less invasive, but there are people who have bad side effects from Lipitor and other drugs and there is an effort now to consider ADT as a first line of treatment for prostate cancer.

    Our community, the prostate cancer survivors community, is preoccupied with PSA screening only and rightfully so, but the problem is broader than ours. I strongly believe that screening is necessary in order to provide the initial information that may lead to further diagnosis and possibly treatment. With no screening our only alternative is to wait for symptoms to start the process and by that time the disease may have progressed and our chance to cure/delay it may be much lower.
    There is no argument that people need to be educated: urologists, primary care doctors and in particular patients. The question is what is the goal and how to structure the education.

    I strongly believe our community needs to fight for continuing screening according to the recommendations of the American Urologists Association, for continuing research that will lead to better diagnosis tools and to educate the people on possible follow up paths to fight Prostate Cancer, including emphasizing diet, exercise, active surveillance. There is no alternative to screening, which is a must, but it doesn’t necessarily need to lead to over-treatment. By the end of the day, each of us needs to decide at every point if side effects out balance the chance to extend life.

    Just of the sake of disclosure: In addition to being a prostate cancer survivor, I am also a stomach cancer (stage 4) patient and I struggle with these questions constantly for both diseases. I can only be sorry that there is no simple test, like PSA, for stomach cancer as well.

  22. Reuven: Your frustration is understandable, and I am in complete sympathy with where you are coming from, but as I keep pointing out, the USPSTF is not suggesting that we abandon the PSA test, It is suggesting that we abandon the thoughtless use of the PSA test — that is a very different message.

  23. More “data” (patients) would speak out against the USPSTF (the panel reporting on PSA screening) if they were alive to do so. And many of the younger men at time of diagnosis who are alive today because of the PSA testing era speak up against the panel recommendation. Any panel considering the PCLO study with 52% contamination of control subjects concluding no significant benefit to PSA screening, because PSA screened men were compared to slightly less PSA screened men, obviously misses the point that PSA screening is valued by patients. Patients dearly want better information and tests but are not willing to put other lives in jeopardy due to some entirely regressive move by the USPSTF.

  24. I am not completely sure that the USPSTF understands that prostate cancer progression can be asymptomatic and “healthy” men are therefore at a risk of an advanced diagnosis with all the consequences that such diagnosis could have. … Which message will be heard by the general population and by those physicians that are thoughtless in the use of the PSA test?

  25. Ralph:

    I am quite ceratin that the USPSTF absolutely does understand that prostate cancer development and early progression can be asymptomatic. These are not stupid people. That is (in my view) exactly why they have left the door open for individual testing in the way that they have.

    The question is would ask is, “Can the survivor community, the advocacy community, and the medical community all now get on the same page and promote the educated use of the PSA test until we have something better?” I can see no good reason not to do this. It would solve a thousand problems.

  26. I appreciate your attempt to search for consensus, but I disagree with that this is really possible unless the draft recommendation is significantly modified.

    The draft says right up front: “The U.S. Preventive Services Task Force (USPSTF) recommends against prostate-specific antigen (PSA)-based screening for prostate cancer. This is a grade D recommendation.”

    And then Grade D is defined below as follows:

    “The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.” And the recommendation for practice is to “Discourage the use of this service”.

    Unless a revised draft includes: (1) a recognition UPFRONT IN THE SUMMARY RECOMMENDATIONS that given the uncertainties, it is rational for many men who have many years of expected lifespan, who are otherwise healthy, who trust their ability to deal appropriately with biopsy results, and who value a reduced probability of death over the risk of side-effects, to opt for PSA testing; and (2) a recommendation UPFRONT IN THE SUMMARY RECOMMENDATIONS that insurance companies continue to fund the testing at the option of the patient, then I don’t see how this current draft merits support.

  27. I can assure you that the USPSTF will never make such a modification. The problem here is that “screening” in epidemiological terms means the regular testing of all men (between specific ages) in order to extend life through treatment on average. The PSA test does not offer such a benefit.

    By contrast, what you are referring to is individual risk-based testing. The USPSTF has already left the door open to this, which is why we need to jump on that opportunity, along with the ACS, the AUA, and as many others as we can get on board..

  28. You say “The PSA test does not offer such a benefit”.

    I think a lot of this rests on what you treat as the null hypothesis. Given the statistical uncertainties, given the lack of long-term follow-up, etc., does the current scientific evidence really say that “There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.” As you point out, the science hasn’t been particularly well-done.

    I think you can make the case that PSA testing has not shown itself to be cost-effective using a 95% confidence interval and a null hypothesis that it has zero effect on mortality. But I don’t see how it can be said that there is “moderate or high certainty that the service has no net benefit.” In fact, for many men, I suspect the 95% confidence interval includes very high net benefits, even from a strict benefit-cost standpoint that includes the cost of medical care in the equation.

  29. Tim:

    I am only telling you what the USPSTF’s asseesment of the sitruation is based on the null hypothesis that PSA testing has (a) no effect on overall mortality and (b) has a signifcviant, demonstrable (and unargued) risk for over-treatment.

    This was what the USPSTF set out to look at, and it is what they have based their recommendation on.

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