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Once more into the screening breach: The New York Times did not kill your patient

One of the more depressing things about getting much more interested in the debate over how we should screen for common cancers, particularly breast and prostate cancer, is my increasing realization of just how little physicians themselves understand about the complexities involved in weighing the value of such tests. It’s become increasingly apparent to me that most physicians believe that early detection is always good and that it always saves lives, having little or no conception of lead time or length bias. Sadly, just last week, I saw another example of just this phenomenon in the form of an article written by Dr. George Lombardi entitled My Patient, Killed By The New York Times. The depth of Dr. Lombardi’s misunderstanding of screening tests permeates the entire article, which begins with his recounting a story about a patient of his, whose death he blames on The New York Times. After describing the funeral of this 73-year-old man who died of prostate cancer, Dr. Lombardi then makes an accusation:

This one filled me with a special discomfort as I knew a secret: He didn’t have to die. I knew it and he had known it. Had he told?

About 5 years ago he had just retired and had a lot more time on his hands. He was a careful man, lived alone, considered himself well informed. He got into the habit of clipping articles on medical issues and either mailing them to me or bringing them in. They came from a variety of sources and were on a variety of topics. He wasn’t trying to show me up. He was genuinely curious. I kidded him that maybe he’d like to go to medical school in his retirement. ‘No’ he laughed, ‘I just like to be in the know.’

When he came in for his physical in 2008 he told me he’d agree to the DRE but not the PSA (his medical sophistication extended to the use of acronyms: DRE stands for digital rectal exam where I feel the prostate with my gloved finger for any abnormality and PSA for prostatic [sic] specific antigen which is a blood protein unique to the prostate and often elevated in prostate cancer). He had read that the use of PSA as a screening test was controversial. This was the year that the United States Preventive Services Task Force, a government panel that issues screening guidelines, recommended against routine PSA screens for older men. It was often a false positive (the PSA was elevated but there was no cancer), led to unnecessary biopsies, and besides most prostate cancers at his age were indolent and didn’t need to be treated. I countered that prostate cancer was the second leading cause of cancer deaths in men and that it was better to know than not to know. This way it would be our decision. The patient with his doctor deciding what was best. But no, he wanted to stick to his guns and since the DRE was normal no PSA blood test was sent.

After describing a conversation with the man’s daughter, who said, “My father was killed by The New York Times,” Dr. Lombardi then goes on to anecdotal evidence and a cherry-picked publication to support his view, quoting an oncologist who says he’s “seeing more men presenting with advanced prostate cancer” and then referring to a single paper in the current Annals of Internal Medicine about PSA screening. Before I look at the article and a recently published paper on screening mammography that made the news, I can’t help but point out that I (mostly) agree with Dr. Lombardi when he says:

Public health doctors, policy experts and journalists tend to look at the population as a whole. It is a better story if it is one story. It makes a better headline. Their statistics are people I sit across from everyday trying to figure out what the future holds. We each have our job to do.

The problem is, of course, that Dr. Lombardi takes that observation and draws the wrong conclusion, namely that his patient died because of lack of screening. He attacks a straw man, sidestepping the true argument, namely that evidence shows that PSA screening probably causes more harm than good for men at average risk of prostate cancer. Unfortunately, Dr. Lombardi obviously does not understand some very basic concepts behind cancer screening, nor does he apparently recognize that doctors who deal with the population-level data that we have regarding screening tests and try to apply them to individual patients are actually looking in a very systematic way about what the benefits of screening are to the individual patient. More on that later. In the meantime, although I wouldn’t go quite as far as Dr. John Schumann did in criticizing Dr. Lombardi, I do view his lament as a jumping off point to look at some recent data on screening for the two most common cancers, breast and prostate.

The problem with screening (yet again for the umpteenth time)

Before I get to my updates on cancer screening, to set the stage I think it’s critical to revisit these two key concepts that you must understand to understand a bit about the difficulties involved in using a screening test to decrease cancer mortality. I’ve explained them both in depth before, so I don’t feel the need to resurrect a detailed explanation again other than to boil them down to two points, with relevant links and illustrative graphs that illustrate the concept. Those who want the more characteristically (for me) verbose versions can follow the links.

First, let’s briefly recap lead time bias, which tells us that earlier detection does not necessarily result in improvements in survival and more successful treatment. In fact, even if earlier treatment has no effect whatsoever on the natural history of a cancer, earlier detection will still give the appearance of an increase in media survival. That increase is simply the “lead time” that comes from detecting the tumor earlier (hence the term “lead time bias”), before it becomes clinically apparent on its own. This concept is illustrated below in these two graphs, first a simpler one:

Lead time bias

And a slightly more complex one:

lead-time-bias

I have explained the concept of lead time bias in more depth here and here, but I do like that graph for illustrating the concept, as well as this one, which demonstrates the effect of lead time bias on a survival curve:

lead_time_bias_02

Perhaps my favorite simple and clever explanation of how lead time bias can result in apparently increased survival rates even if treatment has no effect whatsoever on a cancer’s progression comes from Aaron Carroll. It’s well worth reading.

Now let’s briefly move on to length bias. It turns out that most cancer screening tests have an inherent bias towards detecting more indolent, less deadly cancers because of length time bias. Aggressive, fast-growing tumors tend to go from undetectable to clinically apparent due to symptoms, often already having progressed to an advanced stage, in a shorter time than the time interval between screening tests. These tumors thus do not count as having been detected by the screening test because they go from undetectable to symptomatic between, for example, mammography scans. The slower-growing a tumor is, the longer the length of time between its reaching the minimal detectable size of the screening test and becoming symptomatic, the longer the time there is for a screening test to detect it, as illustrated by these two graphs, beginning with this one:

Length bias

The length of the arrows above represents the length of the detectable preclinical phase, from the time of detectability by the test to clinical detectability. Of six cases of rapidly progressive disease, testing at any single point in time in this hypothetical example would only detect 2/6 tumors, whereas in the case of the slowly progressive tumors 4/6 would be detected. Worse, the effect of length bias increases as the detection threshold of the test is lowered and disease spectrum is broadened to include the cases that are progressing the most slowly, as shown below:

untitled

The other problem with length bias is that the more sensitive the test, the more likely it is to detect indolent tumors that are so slow-growing that within the lifetime of the patient they wouldn’t progress to the point where they would endanger the patient’s life. Some, particularly screen-detected cancers, even spontaneously regress. Such indolent or self-limited cancers do not require treatment, but are frequently diagnosed by screening, a phenomenon known as overdiagnosis. The problem, of course, is that our ability to detect such cancers far surpasses our knowledge of how to predict which ones will regress or remain indolent. So we err on the side of aggressive treatment because we quite reasonably view the consequences of guessing wrong as being so much worse for individual patients than overtreating other patients who don’t require treatment. However, for the average patient, the odds of being helped by a screening test are rather small. For instance, to avert one death from breast cancer with mammographic screening for women between the ages of 50-70, 838 women need to be screened over 6 years for a total of 5,866 screening visits, to detect 18 invasive cancers and 6 instances of DCIS. The additional price of this was estimated to be 90 biopsies and 535 recalls for additional imaging, as well as many cancers treated as if they were life threatening when they are not. For prostate, to prevent one death from cancer, 1,410 men need to be screened over 9 years, for a total of 2,397 screening visits and 48 cancers detected. In other words, screening takes a lot of effort for, on an absolute basis, not as many lives saved as we had hoped. Moreover, in the case of breast cancer, on an absolute scale, the reduction in the risk of dying from cancer is small, as I’ve discussed, and the risks of overtreatment are high.

PSA Screening: Smarter, not harder?

Given that Dr. Lombardi cited it, I thought I’d look at the recent Annals article first. The article comes from a group at the Fred Hutchinson Cancer Center at the University of Washington and is entitled Comparative Effectiveness of Alternative Prostate-Specific Antigen-Based Prostate Cancer Screening Strategies: Model Estimates of Potential Benefits and Harms.

I can’t help but notice, first off, that this is a modeling paper. In other words, the investigators did what the hated U.S. Preventative Services Task Force (USPSTF) did in changing its recommendations for mammographic screening for breast cancer and PSA screening for prostate cancer. They took existing data and ran a bunch of computer simulations in order to model the effects of different screening regimens, noting that they were looking for ways to “screen smarter.” Of course, Dr. Lombardi’s argument is basically a straw man in that no one is saying that PSA screening is necessarily completely useless. What is being said is that there is a significant risk of overdiagnosis, overtreatment, and harm that must be balanced against the relatively small benefit of most of the recommended screening regimens. Back when radical prostatectomy was the preferred treatment for early stage prostate cancer, the risk of harm from overtreatment was significant, up to and including death, but more frequently including complications from surgery, such as incontinence, erectile dysfunction, and other less specific risks of major pelvic surgery, such as injury to the colon, bladder, and other bowel. Later, as radiation therapy supplanted surgery as the preferred treatment for very early stage prostate cancer, the potential complications, such as radiation proctitis. Dr. Schumann described these complications dramatically in his rebuttal to Dr. Lombardi’s article.

In other words, a “one size fits all” approach will not do; we need a more “personalized” approach, if you’ll excuse the term in the wake of its corruption by people like Stanislaw Burzynski. That’s exactly what the investigators on this paper (Gulati et al) tried to do.

What Gulati et al did was to model an large number of screening strategies, thirty-five in all, and then estimate the benefits and harms of each compared to the reference screening strategy of annual screening for patients aged 50 to 74 years with a PSA threshold of 4.0 g/L for biopsy referral. They also tried to validate the models when possible by seeing if it predicts incidence beyond the years of calibration (1975-2000) and to perform sensitivity analyses. Gulati et al summarize their results thusly:

Our results yield several important conclusions. First, we find that aggressive screening strategies, particularly those that lower the PSA threshold for biopsy, do reduce prostate cancer mortality relative to the reference strategy. However, the harms of unnecessary biopsies, diagnoses, and treatments may be unacceptable. Quantifying the magnitude of these harms relative to potential gains in lives saved is critical for determining whether the projected harms are acceptable.

Second, we find substantial improvements in the harm/benefit tradeoff of PSA screening with less frequent testing and more conservative criteria for biopsy referral in older men. These approaches preserve the survival effect and markedly reduce screening harms compared with the reference strategy. In particular, using age-specific PSA thresholds for biopsy referral (strategy 20) reduces false-positive results by a relative 25% and overdiagnoses by 30% while preserving 87% of lives saved under the reference strategy. Alternatively, using longer screening intervals for men with low PSA levels (strategy 22) reduces false-positive results by a relative 50% and overdiagnoses by 27% while preserving 83% of lives saved under the reference strategy. These adaptive, personalized strategies represent prototypes for a smarter approach to screening.

It should also be noted that the decrease in risk of dying of prostate cancer, even under the most optimistic scenarios in the models, was on the orders of a fraction of a percent in absolute terms. Under the models studied by Gulati et al, the risk of death due to prostate cancer without screening was 2.86% but could be reduced to between 2.02% and 2.43%, depending on the model. That’s at most a 0.84% absolute risk reduction, although on a relative scale, a decrease in risk of dying from 2.86% to 2.20% is 29%. The overall conclusion from the modeling study was that it is possible to “screen smarter” if the PSA threshold to refer for biopsy is higher, screening for men with low PSA values is decreased in frequency, and older men, who tend to have elevated PSA anyway, are screened less aggressively. All of these are not unreasonable ideas, and they illustrate the tradeoffs involved in any sort of screening program. They are also far removed from Dr. Lombardi’s straw man characterization of arguments that PSA screening can result in more harm than good as “ignorance is bliss when it comes to PSA screening.”

But what about mammography?

We also screen for breast cancer in women. The preferred test, of course, is mammography, and there is no doubt that regular mammography in women between the ages of 50 and 74 definitely reduces mortality from breast cancer. Of that much, we can be certain, although the risks of overtreatment are not insignificant. Over the last decade or so, the recommendations that screening should begin at age 40, that it should be done annually, and that it should continue for the rest of a woman’s life became the basis of public health policy with respect to breast cancer, as well as breast cancer awareness campaigns by advocacy groups. Then, in 2009, the USPSTF dropped its bombshell, in which it suggested that this screening campaign was too aggressive, resulted in too much overdiagnosis and overtreatment, and should be scaled back. Its recommendation was to begin screening for asymptomatic women at average risk (and this must be emphasized: we’re not referring to women at high risk or women who notice a lump in their breast or other symptoms) at age 50 and to perform it every two years instead of every year. I discussed this when the recommendations caused a stir three years ago, and I stand by what I wrote then.

Interestingly, a recent study from the Breast Cancer Surveillance Consortium published in JAMA Internal Medicine a week ago (Outcomes of Screening Mammography by Frequency, Breast Density, and Postmenopausal Hormone Therapy) seems to support the findings of the USPSTF in 2009. It’s a prospective cohort study examining outcomes of women screened at mammography facilities in community practice that participate in the Breast Cancer Surveillance Consortium (BCSC) mammography registries, and the question to be answered was whether there was a difference in outcomes between women screened on a yearly basis with mammography and women who underwent screening on a biennial basis. Data were collected prospectively on 11,474 women with breast cancer and 922,624 without breast cancer who underwent mammography at BCSC facilities, so this is a large study. The study’s findings are summarized thusly:

Mammography biennially vs annually for women aged 50 to 74 years does not increase risk of tumors with advanced stage or large size regardless of women’s breast density or HT use. Among women aged 40 to 49 years with extremely dense breasts, biennial mammography vs annual is associated with increased risk of advanced-stage cancer (odds ratio [OR], 1.89; 95% CI, 1.06-3.39) and large tumors (OR, 2.39; 95% CI, 1.37-4.18). Cumulative probability of a false-positive mammography result was high among women undergoing annual mammography with extremely dense breasts who were either aged 40 to 49 years (65.5%) or used estrogen plus progestogen (65.8%) and was lower among women aged 50 to 74 years who underwent biennial or triennial mammography with scattered fibroglandular densities (30.7% and 21.9%, respectively) or fatty breasts (17.4% and 12.1%, respectively).

Leading the authors to conclude:

Women aged 50 to 74 years, even those with high breast density or HT use, who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of false-positive results than those who undergo annual mammography. When deciding whether to undergo mammography, women aged 40 to 49 years who have extremely dense breasts should be informed that annual mammography may minimize their risk of advanced-stage disease but the cumulative risk of false-positive results is high.

In other words, in terms of reducing their risk of being diagnosed with an advanced stage tumor or a large sized tumor, it appears not to matter whether women between 50 and 74 undergo mammography every year or every other year. This is not the case when it comes to women between 40 and 49, where less frequent screening is associated with a statistically significant increased risk of being diagnosed with advanced disease. However, one has to balance that with the increased risk of false positive mammography and the absolute risk of dying of breast cancer in this age range, which is only in the range of 0.3%. This is a number that increases with age, but it is still small. For instance, Esserman et al characterized it thusly for a 60 year old woman:

Essentially, mammography reduces the odds of a 60-year-old woman dying of breast cancer in the next decade by 30%. Sounds impressive, until you look at her absolute risk: by getting her annual mammogram, her chances of dying from breast cancer are whittled from 0.9% to 0.6%. Overall, for every 1,000 women in their 60s screened for breast cancer in the next 10 years, mammograms will save the lives of 3 people but 6 others will still die. (The numbers edge up or down in lockstep with a woman’s age.)

As is often the case, this study illustrates the difficulty in balancing the risks and benefits of screening for breast cancer. Remember, the idea behind screening for a cancer — any cancer — is that detecting it early will allow early treatment, better prognosis, and a decrease in the number of people who are diagnosed with later stage cancer, which is more likely to be fatal. As a study that I discussed a few months ago showed, mammography has not reduced the number of breast cancer cases diagnosed at an advanced stage as much as one would expect, meaning that there is significant overdiagnosis. Welch’s study estimated overdiagnosis to range from 22% to 31%. From my reading of the literature, this is only a little bit higher than the rate of overdiagnosis of screen-detected breast cancers that has been estimated, namely around 20%.

The bottom line

Does this mean that we should throw up our hands and stop screening for breast and prostate cancer? Of course not! However, we have to balance the risks versus the benefits in a way that doctors like Dr. Lombardi are seemingly unable to do. Dr. Lombardi clearly views screening as an unalloyed good and believes that his unfortunate patient could have been saved if only he hadn’t listened to the NYT, which described the controversy over PSA screening for prostate cancer, and decided that it wasn’t for him. Never mind those pointy-headed docs in the USPSTF who say that PSA screening for men over 75 can’t be recommended and that balance between the benefits and the drawbacks of prostate cancer screening in men younger than age 75 years cannot be assessed, because the available evidence is insufficient. The American Cancer Society emphasizes that the decision to be screened should involve the man being screened. In any case, the danger of relying on anecdotal information, as Dr. Lombardi apparently does, is that there is no good evidence that PSA screening would have saved his patient’s life. Earlier detection could just as easily have ended up with an apparent increase in survival time that was entirely due to lead time bias. Similarly, those of us who take care of breast cancer patients have to be careful not to be seduced by the idea that mammography is some sort of panacea that will give us power over this dread disease.

The idea that finding cancer earlier almost always saves lives is a seductive one. It gives us, the physicians, the idea that we have power over cancer in contrast to how we frequently feel as though we lack such power. While there is no doubt that screening can decrease mortality from cancer, the devil is in the details. Effect sizes and absolute risk reductions are usually very small, even though they might be fairly impressive as relative values. Screening programs are resource intensive. Most importantly, nothing is free. The benefits of screening do not come without a significant cost in terms of money, overdiagnosis and overtreatment, and psychic anguish. It is entirely appropriate to openly discuss these issues, as it is not possible to have true informed consent on the part of the patient if he or she doesn’t understand the potential risks of screening, so that these risks can be balanced against the not-inconsequential benefits that screening could bring.

I’d like to conclude by putting on my scientist cap. I was once a bit like Dr. Lombardi in that I didn’t think much about screening for cancer and assumed that finding disease early is almost always a good thing. I’ve since come to appreciate that, like many things in medicine, it’s not that simple. Medicine is hard and complicated. Real hard and complicated. It’s very rare that any test or treatment is an unalloyed good or ill. Every test or treatment demands a balance between benefits and risks. Screening is no different. If admitting that to our patients and honestly discussing it with them causes us problems as a physician, then it will just have to cause us problems.

To me, the best solution will come from basic research. The shortcomings of screening, including overdiagnosis, overtreatment, lead time bias, and length bias, are not reasons to give up on screening. They are reasons to learn how to screen smarter. They are also reasons that we desperately need to understand the pathophysiology of the diseases for which we screen. After all, after finding a cancer or ductal carcinoma in situ by mammography, it would be so much better to be able to analyze, for example, its gene expression profile, and to predict whether it’s a cancer that will remain indolent or whether it’s one that’s going to progress rapidly. Prediction based on biology, be it biology as determined by genomic profiling, proteomic profiling, metabolomic profiling, or whatever combination of tests it takes, will allow us to usher in the era of true personalized medicine, in which patients receive treatment as aggressive as their disease’s biology requires or no treatment at all, if their disease’s biology tells us that it’s highly unlikely to end their lives or cause serious disability. I only hope I live to see that day.

In the meantime, we muddle through, balancing benefits and risks as best we can and, hopefully, explaining adequately to patients why we do what we do.

Posted in: Cancer, Diagnostic tests & procedures, Politics and Regulation, Public Health, Science and the Media

Leave a Comment (39) ↓

39 thoughts on “Once more into the screening breach: The New York Times did not kill your patient

  1. kathy says:

    At the risk of sounding like an arrogant little twat, congratulations Dr Gorski on one of the best articles I’ve read in ages. A nice balance of fact and feeling, readable and educational both.

  2. mousethatroared says:

    What an interesting an informative article. I had heard of lead time bias, but I had not heard of length time bias. The explanation really helps in understanding in the complexities of screening programs.

  3. BillyJoe says:

    As David says, Dr. Lombardi is not alone. When the ABC did a piece on prostate screening a year or so ago, many doctors in the online comment section supported their decision to promote prostate screening amongst their patients on the basis of their experience with a single patient who was fortuitously screened and whose life was presumably saved by radical prostatectomy. They seemed not to have even listened to the program which explained the situation very clearly and accurately as David has done above.

  4. rork says:

    Anecdote: Male 54. PSA slowly rising, finally exceeding 5.0, biopsy finds 2/12 cores with high-grade PIN. Doc wants rebiopsy in 8 months, and NCCN guidelines say that too. But it seems too aggressive to me. Surveillance of a worse situation of Gleason 3+3 might advise next biopsy in 12-18 months, but yeah, that’s for a guy perhaps 65 years old. Same stats for age 55 likely advises the knife, but might depend on whether you think they can live to be 75 or not anyway. Tricky enough yet?
    My point is I’m a statistician and can read the papers (but I don’t do prostate research – that’s the guy next door) and it’s incredibly complicated. I really don’t think my doc knows any better than me, and maybe not even the guidelines are that smart – there’s just not that much long term data about people like me (of the right kind). They may be biased toward biopsying too frequently, cause 1) you get too look with something like a gold standard test, which seems good, 2) you do it for a living, 3) not enough data to tell if you are overdoing it so you want to seem cautious about cancer rather than overtreatment, 4) still too influenced by the PSA values (and uncertain how much info is in the velocities), 5) failure to factor in that treatment is nearly inevitable for some of the people, and that for them all the tests are just helping decide when.

  5. Janet says:

    My clinic seems to have recently revised its guidelines to be in line with your conclusions of three years ago–which I shared with them at that time, and to which they responded with indignity and an attitude I would reserve for a response to a homeopath.

    It is because of this blog that I did not react with panic at what was likely an unnecessary biopsy a year ago, so many thanks. :-)

    I want to be clear that I didn’t mind having the biopsy (in a way), just that what I’ve learned here kept me from reacting the way I would have a few years ago, which would have been sheer terror.

  6. WilliamLawrenceUtridge says:

    @BobbyG

    Shakespeare used “breach”. “Breach” refers to a gap in a wall, while “breech” is the back part of something (a gun, or a person). So probably “breach”.

  7. David Gorski says:

    There’s no probably about it; I checked before I hit “publish” because the experience of eight years of blogging told me that if I used the wrong homonym some pedant would nail me for it. (Yes, I have done it before once or twice; each time someone mentioned it without making a substantive comment. Thanks to those experiences and many like them, I now know many of the things that tend to attract the Grammar/Spelling Nazis.) Unfortunately, little did I suspect that even if I used the correct homonym (which I did) some pedant would try to nail me for it.

    Moreover, note to BobbyG: Spelling and grammar flames are incredibly annoying and petty. To me, they serve no purpose other than for the commenter to try to assert his superiority over the blogger, particularly when there is nothing substantive about the actual content of the post included in the comment along with the spelling flame and particularly when they are over one word. They also have a way of derailing the comment thread to absolutely no useful purpose. Sorry if I’m being harsh (actually, I’m only a little sorry), but spelling and grammar flames quite rightly are considered very, very weak and pointless:

    http://redwing.hutman.net/~mreed/warriorshtm/grammarian.htm

    Nobody wins as a Grammar Nazi. Don’t believe me? Check out this video:

    http://www.collegehumor.com/video/6060107/grammar-nazis ;-)

    On that note, please, back to substance, please. No more spelling or grammar flames.

  8. WilliamLawrenceUtridge says:

    Or you might want to do what I do, and report minor things like typos to the typo-fixer. Head to the Contact us page and search for “Please report typos, errors and other glitches to”.

    I feel sorry for Paul for saying it, but having this notice just above the comments section would probably prevent comments like this.

  9. mousethatroared says:

    It is interesting to note, however, I think due to the “ea” in breach, each time I see the headline I read “Screaming Breach”, then have to correct myself. Clearly, not a phenomenon* that an author could correct for…and it does lend a certain drama to the reading experience….

    *or possibly even a phenomenon that happens to anyone else but me.

  10. mousethatroared says:

    and when I say interesting, I mean, probably not very interesting.

  11. David Gorski says:

    I feel sorry for Paul for saying it, but having this notice just above the comments section would probably prevent comments like this.

    Sadly, from my eight years at the blogging biz, I can say that I’m pretty confident that it wouldn’t.

  12. tmac57 says:

    Should a family history of a relative dying early from prostate cancer (say a paternal grandfather) influence whether or not to screen?

  13. rork says:

    tmac57: yes. Your dad’s data might be more interesting. Mine died at age 45 (of war) long ago so no data. My brother’s been under the knife (at age 50), so the docs treat me closer to “inevitable”. How much influence should those have on you: for dad’s dad, not too much. Hard to quantify is an understatement.

  14. windriven says:

    @WLU

    “Sadly, from my eight years at the blogging biz, I can say that I’m pretty confident that it wouldn’t.”

    Hmmm, perilously close to Crislip’s Law.

    For what it is worth, I agree with you. I was too dim to know there was a contact address for errata until you noted it. For many of us spelling and grammar nazis the only objective is to polish the perfect to the flawless. SBM isn’t ephemeral. People read old blogs – as good a proof as any of SBM’s worth. To some of us that longevity suggests value in cleaning up minor textual flaws.

  15. WilliamLawrenceUtridge says:

    I can’t take the credit for that, it was Dr. Gorski’s point :)

    I think as spectators it’s very easy for us to comment on trivialities of spelling and grammar (much as these corrections do improve the post, IMO). But truly it does divert from the content, to no good end. Were I the author of the post and someone completely glossed over the main points to pedant over the spelling errors, I would doubtless be irked as well. Extended over years, and thousands of posts, I would expect it to be a button issue for me as well!

  16. art malernee dvm says:

    I “believe” I read somewhere that prostate removal when you get prostate cancer decreases the chance of dying from prostate cancer but your life expectancy is the same without surgery. The unproven theory was the prostate has some unknown life extending ability thus increasing the risk of dying from other things when it was removed. is this why radiation is now the treatment of choice?

  17. Quill says:

    Thank you for this most informative article. I appreciate such frank discussions of complexity in medicine and how that applies to patients looking for diagnosis. There is a David Bowie song with the exclamatory line “I don’t want knowledge! I want certainty!” This seems to apply to much human behavior, including doctors and patients, when it comes to the results of screening tests and whether or not to use them. The best knowledge so often includes a lot of uncertainty and it seems hard to live with it unless you really understand the situation. This article helps in that understanding.

  18. David Gorski says:

    There is a David Bowie song with the exclamatory line “I don’t want knowledge! I want certainty!”

    I think I entitled a post “I don’t want knowledge! I want certainty!” once, although I can’t remember if it was here or at my not-so-super-secret other blog and I don’t have time right now to look it up. Off to work again…

  19. Quill says:

    By David Jones, you did epigraph such a post:

    http://www.sciencebasedmedicine.org/index.php/certainty-versus-knowledge-in-medicine/

    I hadn’t seen that before, but having just read it, I am happy that it compliments today’s article.

  20. BrewandFerment says:

    @Janet,

    Hear, hear. I got the same sort of response from a mammo center even more recently when I tried to wave the Mar 13 Consumer Reports at them while trying to fend off a biopsy the very next day after the mammo. I lacked the smarts about this blog at the time and was just insecure enough in the face of strong pressure from the radiologist (head of the center at that!) that I failed to hold my ground and so submitted to the biopsy without insisting on–at the very least–a second opinion on the radiology report or even a chance to catch my breath and talk it over with my PCP. I still have a hard time getting my head around the fact that up until the mammo and biopsy, owing to among other things breastfeeding 3 kids for a combined total of 8 years, I went from lower than average risk to high risk because the pathology report said it was Atypical Ductal Hyperplasia. No matter what, there was no excuse whatsoever for the excessive urgency and fear-mongering approach at the mammo center so I fired them and will go elsewhere next time.

    After all is said and done, I still wish I had never seen the inside of a mammography center until I turned 50 this year as recommended by USPTF and Canadian/European health programs. Now I gotta figure out what to do on colonoscopy too, although it seems to be less problematic than mammos for the overdiagnosis/overtreatment issues. I read all the pertinent English stuff at Nordic Cochrane, too, and find it very thought provoking.

  21. Newcoaster says:

    I agree with you David that many physicians themselves don’t understand the role of “screening tests”, which tests are appropriate, or how to interpret them. Thinking back on my own training, I don’t really remember learning much about them in medical school either, or it was in a Statistics class, so my mental eyes glazed over. I’m not sure there were that many screening tests 20 years ago.

    What I know about screening tests I have learned myself since going into practice. A week doesn’t go by that I don’t have arguments….er….discussions with patients waving some article from a magazine or newspaper, or some email they got from a “concerned friend….please forward to all your friends because YOUR DOCTORS DON”T KNOW……” Sigh.

    I’ve never been on the PSA bandwagon, and that is the most common screening test I have disagreements with. Interestingly, many of the disagreements are with specialists. Urologists see a skewed patient profile, and they forget that all their patients have been pre-selected and come with either a disease, or a constellation of symptoms or abnormal tests. In their practice, it makes sense that every patient gets annual or bi-annual PSA testing. In my family practice, that vast majority of men don’t need it, for all the reasons you have gone into.

    Women keep showing up wanting a CA 125 test for “ovarian cancer”. They are usually very upset to find out that there is no screening test for ovarian cancer, and no, I won’t order it just because they want it or their chain e-mail tells them I’m a bad doctor if I don’t.

    Unfortunately, I know there are doctors who will order tests just based on patients requesting them. These are usually the same doctors who order labs requested by Naturopaths, Xrays wanted by Chiropractors, and don’t have a problem making referrals to acupuncturists because the patients health plan covers acupuncture.

  22. Narad says:

    each time I see the headline I read “Screaming Breach”

    Now I’m stuck with “Once more screening into the breeches.”

  23. lilady says:

    @ BrewAndFerment: I had a similar experience last week at the large radiology center that I have been using for several years. I went for my yearly mammography on Tuesday, received a phone call from the center for a follow-up left breast 3-D mammography and sonogram the following day, and had the tests on Thursday. On Thursday I had the radiologist’s report that found a DENSE 6 mm nodule on my left breast…the first “abnormal” mammography for me. Walking through the back halls of the Center (in between the 3-D mammography suite, toward the sonogram suite), I spotted a large specimen box, marked “breast biopsy specimens”. I, of course, inquired if breast biopsies were done at the Center, and was told “yes, on certain days”.

    Question: Is this a new type of service, now offered by large radiology practices? I would assume that a breast cancer surgeon does the biopsies, not a radiologist….?

    I am wondering why anyone would agree to having a breast biopsy, done by a physician who is unknown, without a referral from their primary care provider and without checking the physician’s “credentials” and speaking to friends who have undergone biopsies and surgeries for breast cancer.

    I’m so grateful that the radiologist told me the results immediately…that the DENSE nodule is a cyst.

  24. lilady says:

    P.S. Thanks to Dr. Gorski, for explaining the new recommendations about spacing of mammograms for women who are low risk.

  25. WilliamLawrenceUtridge says:

    Pink Ribbon Blues by Gayle Sulik, spends a lot of time exploring the issues involved in diagnosing breast cancer, lead time bias and whatnot, particularly going into explaining how DCIS and another condition I forget now are inflating statistics about breast cancer. It also goes into how pink ribbon culture isn’t as helpful as you might think. Interesting book, a bit of a slog though. Quite iconoclastic.

  26. mousethatroared says:

    One thing that I’m curious about with prostate cancer. Do symptoms often, sometimes, seldom (?) provide any help with detection and does the presence of symptoms give a doctor any information on whether to treat the cancer or not? My dad had prostate cancer around twenty years ago. I’m pretty sure that the cancer was found based on his complaints of symptoms. I suppose it’s somewhat ironic, with all the commentors talking about doctors over-reacting to test results, but my dad wasn’t informed that he had cancer for a year. The doctor who did the biopsy thought his family doctor would tell him, the family doctor thought the other doctor would tell him…

    Anyway, he had prostate surgery and had some of the expected side effects of the surgery which lowered his quality of life, somewhat. He died 6 years ago of lung cancer, although he was very healthy and vigorous up until 4 or 5 months before his death. I wonder if today they would have recommended that prostate surgery based on his symptoms (difficulty with urination) and if not, what the results would have been. Hard to tell, I’m sure.

  27. dinseattle says:

    Well I feel like the poster child of mammogram overtreatment. A 4 mm cluster of calcifications, BI-RAD4, so I had the core needle biopsy. First, the diagnostic mammogram caused intense pain, such that it still hurt to walk a week later when I had the CNB. That sort of internal bruising can’t be good for the breast.

    Second, the CNB consisted of a surprising to me amount of radiation. After the procedure, during the followup regular mammogram, I asked. She took 18 images. But then, while my bleeding was being addressed, the radiologist came back and said oops, we missed the target cells and want to do it again. So I succumbed. Even more radiation. I then asked if the center (part of my primary care doctor’s circle of electronic records) keeps track of lifetime radiation exposure and was told no. I did point out to the technician who had actually taken all those images that it was pretty ironic that they do all this radiation where they know 80% of them are not cancer. She claimed the radiation was such small risk, but admitted that it wasn’t no risk. But they are taking an area of suspicious cells and bombarding it with radiation. How is that not increasing lifetime cancer risk? She kinda looked startled, as if she had never thought of that before.

    (And in fact, on the cancer risk calculator, simply having a CNB increases one’s risk of breast cancer. Why is that?)

    A week later I got the results. Flat Epithelial Atypia. And my reading all pointed to it being an indolent non-obligate precursor to the low grade DCIS. Recommendation was follow up surgical biopsy (even though in the literature that’s controversial). When I saw the surgeon and confirmed that FEA was all that was found, no ADH, I said I didn’t want a biopsy, I wanted watchful waiting. He then admitted that their radiology group (without consulting the oncology staff) had decided not to use BI-RAD3 category any more, because women just didn’t like waiting 6 months (or they were worried about lawsuits or something). I have tried to contact the radiologist who gave me the BI-RAD4 to confirm this or to confirm what aspects of the picture actually put me in the BI-RAD4 category, but he didn’t return my call. I will be going back for the 6 month followup in another couple months and will schedule for a day when he is also scheduled.

    So the oncology surgeon was semi-ok with me not having a biopsy. Not really though. I pointed out to him that a Canadian Breast Cancer site I found said FEA meant watchful waiting, not further treatment. He and I had a bit of a chuckle over the difference between US and Canada. But then at the end he asked his assistant to provide me with some more literature on FEA. Well, the internet pages she printed out for me were from that very website. She said it was a good site in general and that there wasn’t anything else she could find written for lay people on FEA.

    The surgeon wanted to see me in a month, perhaps to see if I changed my mind. I hadn’t. At that point he was more agitated with me not succumbing to the knife and insisted I meet with the medical oncologist to get me on tamoxifen (or the aromatase inhibitors, depending). But he was also pretty good about strategizing the next year. The 6 month mammo, the radiologist would probably freak, he said. But I shouldn’t. Unless there is something major to see, I should then wait 6 more months to see what the picture shows. And at that point (due to my further menopause status and perhaps also due to the tamoxifen I am not taking) my breasts should be less dense (they are in the 50% category) and if there’s a concern, that would be a better time for an MRI, which has higher rates of false positives with denser breasts. He’s in an odd place of agreeing with me that I am probably the result of overtreatment, but also wanting to Do! Something! Doesn’t want me to get cancer on his watch, is the way he put it. Well, if I had a stroke, there’s no proof that the tamoxifen caused it, and I wouldn’t ever see him anyway so he’d never know, would he?

    The medical oncologist was also perplexed about what to do with a diagnosis of pure FEA. She agreed with me that tamoxifen was overkill. I showed her a Decision Aid for taking tamoxifen I had gotten from the NIH website that showed that tamoxifen for preventing recurrence of cancer will reduce cancer recurrence by 8 women in 1000 and will cause stroke or thrombosis in 8 women out of 1000. She hadn’t seen that website before, but didn’t seem surprised with the conclusion. And I don’t even have cancer, just an indolent precursor.

    I haven’t even mentioned that the breast with the two CNBs hurt like hell for a month. So much that I was inactive and gained 3 pounds. Stress and spending so much time researching breast cancer on-line didn’t help that either. And now 4 months later I still get occasional stabbing pains.

    Oh, and the reason for my succumbing to the not quite every year (I stretch it out as long as I can) mammogram is a compromise with my primary care doctor. When I had pointed out to her the evidence that screening had some flaws, she got agitated and said “I had a patient DIE from DCIS!” At that point I knew I could not have a rational conversation with her about the statistics.

    In my reading, I have found a link between metabolic syndrome and breast cancer. I find it interesting that the clinical trials are looking at metformin and no clinical trials on drastic lifestyle measures to control hyperinsulinemea to prevent recurrence. Now I am in the high normal BMI category, but I struggle with weight, fatigue and mood. Also, everyone in my family is obese and type 2 diabetic or getting there. Grandparents, mother, aunt and uncle all died of causes relating to diabetes. Last time I had blood panel, my fasting glucose was a little elevated, but the doctor said not to worry about it because my cholesterol scores were so good. And neither the oncological surgeon nor the medical oncologist mentioned metabolic syndrome issues as an alternative preventative measure to the tamoxifen, even though they took a family health history. If they had looked they would have seen the red flag there. I suppose I just do not look like someone at risk? If I did look like someone at risk, would they have suggested metformin or something then? I don’t know.

    So, for the last few months, I have avoided sugar and refined carbs, have lost 13 pounds and mood has improved as well as energy. Instead of having to force myself to get out and walk and jog a bit, I am now running regularly, did a 5K and signed up for a half marathon in June. I feel good. Perhaps this debacle was the tipping point for me to take my diet and lifestyle more seriously, for positive effect.

    I do have a question for Dr Gorski. In a previous post, you mentioned that autopsy studies showed a disease reservoir of DCIS to be very high, 39% of women 40-50 showed signs of DCIS. I cannot find that information elsewhere and would be most obliged for a pointer to the studies. Many thanks.

  28. BrewandFerment says:

    @lilady,

    “Question: Is this a new type of service, now offered by large radiology practices? I would assume that a breast cancer surgeon does the biopsies, not a radiologist….?”

    Well, it appears to be offered here at this practice that is a subset of a largish (or perhaps for this smaller urban area it’s large, I originally come from a much bigger city so I still have smaller city confusions like “traffic” and “rush hour” that don’t even come close by my previous locales) medical practice. My sister in TX assures me that it can’t be done there by radiologists as that counts for self-referral and is not allowed.

    “I am wondering why anyone would agree to having a breast biopsy, done by a physician who is unknown, without a referral from their primary care provider and without checking the physician’s “credentials” and speaking to friends who have undergone biopsies and surgeries for breast cancer.”

    Ummm….well, truth be told, I beat myself up pretty hard for that as alluded to by my comment that “I failed to hold my ground” but then when the aforementioned Consumer Reports discussed an MD who nearly died of sepsis from a prostate biopsy having caved into pressure for said biopsy, I felt a little less bad. I guess combined with the extreme pressure and urgency conveyed by the radiologist–words like “now don’t you skip out on me” as her parting comment after she scheduled me for a Friday (mammo was Wed) biopsy–and the immediate session with a nurse case manager to go over preps for the biopsy, etc–fright was kicking in and my normally argumentative evil twin must have been in hiding. The next day I called back the case manager with some questions which had occurred to me in the night, and was given even more encouragement to attend that very day because there had been a cancellation so that it could be accomplished by the same radiologist. I had to scramble to get transport–husband is not a cellphone user and was out with the car for the day; eldest child only had a short time between classes and work to bring that vehicle home for my use–so I am still occasionally kicking myself for not saying, no, too hard for the Thurs (day after) biopsy and then contacting my PCP.

    It was all part of the One Stop Shopping experience that the Breast Health Center has been touting as their pride and joy, I think. They said they would call my PCP for authorization–I found out later that the radiologist only spoke to the insurance wrangler, not my PCP! And then when I actually arrived and got “there’s no more time for arguing, this must be done” I guess my best intentions just went out the window. As I told the center when I sent them a request to discharge me from their care and send my images to me (BTW, that and mammo reports were all I’ve received to date since the 1/30/13 biopsy, no letter or other “sorry you were unhappy” or anything) because of their clearly unjustified rush and pressure, I will find it harder to accept other recommendations even when speed is more important. Hopefully I will be able to put it aside and know the difference.

    I did get a second opinion when I attended preliminary planning to see if I would qualify for a study at a major medical school of high repute, and there the radiologist who read a fresh mammogram said he would not have biopsied so quickly as the lesion was very small, and that there was nothing else of interest around the marker clip placed by the radiologist. He did note, wryly, that it’s rare to find someone complaining of possibly being treated too much instead of unhappy with delays.

  29. BrewandFerment says:

    @lilady,

    and you know what’s worse? There was NEVER any encouragement to talk to my PCP! And when I arrived at the biopsy and was clearly agitated–the tech saw blotchiness on my chest and asked if that happened when I was upset, which I wasn’t aware of–no one even then either suggested I call my PCP or took my blood pressure. When I went in to see the PCP the next morning (after the fact, oh so unfortunately) my BP was something like 160/90 (taken manually) when it is almost always 120/68 or so.

  30. BrewandFerment says:

    @lilady,

    Oh and the fact that the radiologist was the director of the center made the pressure even worse. I knew who she was because her name was on the door to the center as such.

  31. David Gorski says:

    Question: Is this a new type of service, now offered by large radiology practices? I would assume that a breast cancer surgeon does the biopsies, not a radiologist….?

    In the old days, surgeons did nearly all the biopsies, but that’s changed a lot over the last 20 years. These days, most breast biopsies are image-guided needle core biopsies. The imaging used to guide the biopsy can either be ultrasound (used for masses visible on—of course—ultrasound) or mammography (which is used to biopsy microcalcifications, which usually can’t be seen adequately on ultrasound). The former procedure is called an ultrasound-guided biopsy, the latter, a stereotactic biopsy. A lot of breast surgeons do ultrasound-guided biopsies, but so do radiologists in women’s imaging centers. Overall, it’s mostly radiologists who do ultrasound-guided biopsies, but surgeons do quite a few of them too in their offices because ultrasound equipment is pretty inexpensive and small and surgeons are more than capable of doing this procedure if they are trained in it. In contrast, stereotactic biopsies are almost exclusively the purview of radiologists these days because they control the equipment, which is a lot more expensive and bulky. Very few surgeons do them, and one of the biggest issues in breast surgery fellowship programs is getting trainees the required exposure to doing stereotactic biopsies.

    In general, the metric we look at (at least in Michigan) is that no more than 15% of breast biopsies should be surgical biopsies any more. At our center (and, I daresay, most centers with a good radiology group and dedicated breast surgeons), it’s much less than 15%.

    It should also be noted that radiologists can’t just do a biopsy after noting an abnormal mammogram or ultrasound. They need an order the doctor who ordered the imaging study in the first place. Of course, there are lots of radiology practices that are tight with networks of physicians; so, depending on the specific situation, getting the order can be a matter of a quick phone call to the ordering physician’s office to inform the doc of the abnormality and ask for an order. Then there’s getting approval from the insurance company, but I won’t go there now…

  32. pmoran says:

    Then there’s getting approval from the insurance company, but I won’t go there now…

    While breast screening is often performed privately in Australia, it is mainly carried out via free, government-run, stand-alone clinics — as I think also applies in many European countries.

    This is a near-ideal arrangement. It favors cost-effectiveness, strict adherence to evidence-based guidelines, good information-gathering and hence optimal quality assurance, and the reduction of the distorting financial incentives and the sometimes variable quality of services that can exist within fee-for-service systems.

    The only major downside was that results filtered through to the patient rather slowly.

  33. lilady says:

    @ BrewandFerment/Dr. Gorski: My GP and all the specialists my husband and I have ever used are affiliated with a large teaching hospital. The 6mm DENSE nodule, if it was not a cyst, would have required a needle core biopsy using ultrasound imaging. I would never agree to any biopsy unless I had first chosen/consulted with a breast cancer surgeon.

    Dr. Moran, I asked to speak with the radiologist (after the 3-D Mammography…and before the ultrasound) and the radiologist was summoned into the ultrasound suite to give me the “good news”. I was happily surprised that she gave me the results. Thinking back, I “suspect” that I would have told that the written reports would be sent to my GP…if I required a biopsy because the tests did not R/O cancer. I have excellent complete medical and drug coverage, (Medicare and secondary “gap coverage).

    BTW, dear hubby went to our GP today, with a complaint of pain and “burning” in the groin area and a h/o of bilateral inguinal hernia repairs ~ 20 years ago. Our G.P. is convinced he now has a testicular hernia. Sooo…back again to that same large radiology center for a testicular ultrasound. Only the breast radiologist was around, so he didn’t get any results. We both think he will be undergoing hernia repair…soon.

  34. BillyJoe says:

    Michelle,

    Coincidentally, my father also had prostate cancer and he also died of lung cancer but, in his case it was all telescoped into about six months. But the fact that he had prostate cancer meant that I had to make a decision regarding prostate screening, As a result, I know a bit about prostate conditions.

    So, as to your question, prostate cancer rarely causes symptoms until advanced. The first symptoms are often due to spread of the cancer to the spine causing back pain. Prostate symptoms are much more likely to be caused by BPH even when investigation reveals prostate cancer is also present.

    The surgery is also different. Radical prostatectomy for prostate cancer (provided the tumour is confined within the prostatic capsule). Trans-urethral resection of the prostate for BPH – only the inner part of the prostate is removed to relieve obstructive symptoms and the removed prostatic tissue can coincidentally reveal the presence of prostate cancer.

    (My decision regarding screening: based on the fact that screening is very unlikely to save my life but is reasonably likely to leave me impotent or incontinent or both, I decided not to undergo screening.)

  35. mousethatroared says:

    @BillyJoe – Thanks – that does lead me to other questions, but as I said in the other thread. I’m feeling rather sh*&tty, so I won’t pursue it. It is good to hear that you are thinking through your options, though.

  36. Tim Bartik says:

    Dr. Gorski:

    You make some good points in this post about lead time bias, and about screening having both harms and benefits. However, I believe that some of your points about the debate about prostate cancer screening are incorrect.

    1. You state that the USPSTF has said that the evidence is insufficient about prostate cancer screening for men less than 75. That was their 2008 position. Their new position as of 2012 is that we shouldn’t do prostate cancer screening for any age.

    2. The Hutchinson group at the University of Washington is clearly at wide variance with the USPSTF on the relative benefits vs. costs of prostate cancer screening. This is clearly the case in a recent point-counterpoint between the HUW group and the USPSTF in the journal Medical Care, in the April 2013 issue. The HUW group’s position is stated at http://journals.lww.com/lww-medicalcare/Abstract/2013/04000/Limitations_of_Basing_Screening_Policies_on.2.aspx
    with a follow-up response from folks from the USPSTF, and then a rebuttal by the HUW group.

    3. But the different positions can clearly be seen in the paper you reviewed by the HUW group. You cited some stats that claim that to eliminate one death from prostate cancer by doing screening, you will end up detecting an additional 48 prostate cancers. The USPSTF cited similar statistics. But the HUW group’s simulation studies say this is misleading because it doesn’t look at what happens after the random assignment experiments with screening have stopped. The HUW Annals study you cited, for example, found that for the most aggressive prostate cancer screening strategy they considered, the resulting reduction in the risk of death from prostate cancer is from 2.86% to 2.02%, or 0.84%. But for this strategy, they estimate that the additional prostate cancers detected that otherwise would not have detected is about 6% for all men screened. The ratio of additional cancers detected to lives saved is 7.08 to 1. This is quite different from the 48 to 1 figure you cited, and similar figures cited by the USPSTF.

    4. I think which ratio is right makes a big difference. If we assume that all these cancers are treated, and that half of all men treated suffer serious side-effects such as incontinence and impotence, then the 48 to 1 ratio you and the USPSTF cite implies a ratio of serious harms to lives saved from prostate cancer screening of 24 to 1, which seems to make screening a bad idea. But if the ratio is 7.08 to 1 (or even less under other screening strategies), then the ratio of serious harms to lives saved is about 3.5 to 1. With that ratio, I think screening seems like a much better idea, although we might want to adopt smarter screening strategies to reduce that ratio still further. (And, in addition, we might want to adopt smarter treatment strategies, such as encouraging active surveillance in lower-grade prostate cancer, which would also reduce the harm to benefit ratio.)

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