written by reader Pros & Cons of Screening for Breast and Prostate Cancer

The old news, by now a couple of years old, is that the U. S. Preventive Services Task Force (USPSTF) has recommended against routine screening of women aged 40 to 49 years for breast cancer, and also recommended against screening for prostate cancer for men at any age using the prostate-specific antigen (PSA) test.

The newer news is that a lot of the evidence, perhaps most of it, appears to be contrary to the USPSTF’s recommendations. And the big question is, why did the USPSTF come to these conclusions?

Who, or What, Is the USPSTF?

Here’s what they say about themselves:

“U.S. Preventive Services Task Force

The USPSTF is an independent panel of non-Federal experts in prevention and evidence-based medicine and is composed of primary care providers (such as internists, pediatricians, family physicians, gynecologists/obstetricians, nurses, and health behavior specialists).

The USPSTF conducts scientific evidence reviews of a broad range of clinical preventive health care services (such as screening, counseling, and preventive medications) and develops recommendations for primary care clinicians and health systems. These recommendations are published in the form of ‘Recommendation Statements.’

AHRQ’s Prevention and Care Management Portfolio provides ongoing administrative, research, technical, and dissemination support to the USPSTF.

About the USPSTF

The USPSTF strives to make accurate, up-to-date, and relevant recommendations about preventive services in primary care.

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To learn more detailed information about the USPSTF, including how it operates, current members and partners, and background information, visit http://www.uspreventiveservicestaskforce.org/about.htm

Methods and Processes

For the USPSTF to recommend a service, the benefits of the service must outweigh the harms. The USPSTF focuses on maintenance of health and quality of life as the major benefits of clinical preventive services, and not simply the identification of disease.”

AHRQ, by the way, is the Agency for Healthcare Research and Quality, which is part of the U. S. Department of Health and Human Services. Nobody, as far as I can tell, has accused either the USPSTF or the AHRQ of not being conscientious and on the up & up. My ornery turn of mind, however, suspects the USPSTF of keeping a sharp eye on healthcare costs in general, and of being perhaps excessively reluctant to recommend treatments or procedures that, although they might benefit some patients, cannot be demonstrated to meet certain standards of cost effectiveness. That might be my prejudice, but let’s see how their recommendations stand up in the light of the evidence.

The Mammography Recommendations

Back in 2002, the USPSTF issued a recommendation for screening mammograms for all women 40 years of age or older. The recommendation went on to say that

“Clinicians should inform women about the potential benefits (reduced chance of dying from breast cancer), potential harms (for example, false-positive results, unnecessary biopsies), and limitations of the test that apply to women their age.”

However, in November of 2009, they issued an update:

“The USPSTF now recommends against routine screening of women aged 40 to 49 years (C recommendation), recommends biennial screening mammography for all women aged 50 to 74 years (B recommendation), and provides an I statement regarding screening for women older than 75 years.”

Here, by the way, if you’re interested, is what the USPSTF says those recommendations mean:

What the Grades Mean and Suggestions for Practice

Grade

Definition

Suggestions for Practice

A

The USPSTF recommends the service. There is high certainty that the net benefit is substantial. Offer or provide this service.

B

The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Offer or provide this service.

C

Note: The following statement is undergoing revision.
Clinicians may provide this service to selected patients depending on individual circumstances. However, for most individuals without signs or symptoms there is likely to be only a small benefit from this service.
Offer or provide this service only if other considerations support the offering or providing the service in an individual patient.

D

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. Discourage the use of this service.

I Statement

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Read the clinical considerations section of USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms.

Talk about carefully hedged! But now, let’s take a look at the “evidence” that they themselves cite:

They base their conclusion on several clinical trials and meta-analyses. (A meta-analysis combines the results from several trials or studies, even if the ground rules by which the trials were conducted are different – i.e., patients of different ages or with different risk factors, etc.) In women in their 40s who were screened via mammograms, the risk ratios for death from death cancer in these studies averaged 0.85, meaning that they had a 15% reduction in breast cancer mortality, compared with the women who had not had mammograms. That’s not nothing!

Here are the pooled results (USPSTF figures) for four age brackets:

Table 1. Pooled RRs for Breast Cancer Mortality From Mammography Screening Trials for All Ages

Age

Trials Included,
n

RR for Breast Cancer
Mortality (95% CrI)

NNI to Prevent 1 Breast
Cancer Death (95% CrI)

39-49 y 8* 0.85 (0.75-0.96) 1904 (929-6378)
50-59 y 6a 0.86 (0.75-0.99) 1339 (322-7455)
60-69 y 2b 0.68 (0.54-0.87) 377 (230-1050)
70-74 y 1c 1.12 (0.73-1.72) Not available

CrI = credible interval; NNI = number needed to invite to screening; RR = relative risk.
* Health Insurance Plan of Greater New York,27 Canadian National Breast Screening Study-1,28 Stockholm,26 Malmö,26 Swedish Two-County trial (2 trials),26,31 Gothenburg trial,30 and Age trial.29
a Canadian National Breast Screening Study-1,28 Stockholm,26 Malmö,26 Swedish Two-County trial (2 trials),26,31 and Gothenburg trial.30
b Malmö26 and Swedish Two-County trial (Östergötland).26
cSwedish Two-County trial (Östergötland).26

The last column is where we find the data that pushed the USPSTF over the edge. NNI, in case you missed the tiny footnote, is the “number needed to invite to screening” to prevent one breast cancer death. Whereas for women aged 60 to 69, that number is 377, and for women aged 50 to 59 it is 1339, for women aged 39 to 49 it is 1904. What the USPSTF is saying is that it’s not worth screening 1904 women in their 40s to prevent one death, whereas it is worth screening 1339 women in their 50s and 377 women in their 60s to prevent one death. It seems to boil down to an economic calculation.

Now, according to the U. S. Census Bureau, in 2011 there were 21,604,000 women in our country between the ages of 40 and 49. My little pocket calculator, which has never lied to me, tells me that if all these women had mammograms, it could result – if you trust those figures from the USPSTF – it could result in preventing 11,347 deaths from breast cancer

I feel like putting that in large bold type: mammograms for women in their 40s could result in preventing 11,347 deaths from breast cancer.

So why did they change their recommendation? Let’s take a look at the “harms” they mention as offsetting the benefits (i.e. not dying of breast cancer). These harms include radiation exposure, pain during the procedure, anxiety and distress, and possible false positives resulting in unnecessary biopsies. They themselves minimize the risk of radiation exposure, note that few women consider the pain as a deterrent from future mammograms, and state that false-positive mammograms had no consistent effect on women’s general anxiety and depression. Are those “harms” enough to recommend that women in their 40s forego a procedure that could save their lives?

In the meantime, what has been happening is that the number of screenings has been declining, and along with that, the number of cancers detected has been declining. For example at the New York Presbyterian-Weill Cornell Medical Center from 2007 through 2010, 43,351 screenings were done and 205 breast cancers were found, 19% of which were in women in their 40s, and half of that 19% were of the invasive type. Those are cancers that spread through the breast tissue rapidly and need to be treated promptly, but, of course, if they are not detected they won’t be treated. In another study, researchers found that mammograms increased at a rate of 0.9% yearly from 2006 to 2009, but when the USPSTF recommendations were issued in 2009, the rate of mammography declined by 4.3%. That means fewer cancers detected, fewer cancers treated, and more deaths.

My take on this: the recommendations of the USPSTF in this particular case have done more harm than good.

And Now, What About Prostate Cancer Screening?

That issue is a good deal more complicated, and I won’t be doing anyone any favors by waltzing over the difficulties. These come bubbling up from two sources – one, the disease process itself, and two, the nature of the prostate specific antigen (PSA) test.

Here’s the thing about prostate cancer: it mostly affects older men, and it progresses fairly slowly. The statistics are illuminating. The median age for diagnosis of prostate cancer is 66, less than 1% of the cases are seen in men younger than 44, and less than 10% in men younger than 54. According to SEER data (Surveillance Epidemiology and End Results, from the National Cancer Institute), prostate cancer mortality is 23 per 100,000, but in black men it’s more than double that – 50.9 per 100,000. The reasons for this huge discrepancy are not entirely clear, but the guess is that it has a lot to do with both treatment and screening.

In many cases prostate cancer progresses quite slowly. The common wisdom is that men die with it, but not of it. Something else gets us first. However, this may be changing – as mortality diminishes from other common diseases such as heart disease and stroke, many men live longer, giving even slow-growing prostate cancers time to grow and become fatal.

And, here’s the thing about the PSA test: it’s not very good, either in terms of sensitivity or specificity. The test has been in use since 1986, and for much of that time doctors thought that a level of 4.0 ng/mL (nanograms per milliliter) was the cut point for a follow-up. However, men with a condition called benign prostatic hyperplasia (BPH) can have elevated PSA levels, as can men with urinary tract infections. And some men can have prostate cancer without having elevated PSA levels. So, what’s to be done? Toss the whole thing in the garbage can and trust that we’ll be struck by lightning before prostate cancer gets us?

That’s not quite what the USPSTF says, but it amounts to the same thing:

Screening for Prostate Cancer

Current Recommendation

Release Date: May 2012

  • The USPSTF recommends against PSA-based screening for prostate cancer.
    Grade:
    D Recommendation.

This recommendation applies to men in the general U.S. population, regardless of age. This recommendation does not include the use of the prostate-specific antigen (PSA) test for surveillance after diagnosis or treatment of prostate cancer; the use of the PSA test for this indication is outside the scope of the USPSTF.

Prostate cancer is a serious health problem that affects thousands of men and their families. But before getting a PSA test, all men deserve to know what the science tells us about PSA screening: there is a very small potential benefit and significant potential harms. We encourage clinicians to consider this evidence and not screen their patients with a PSA test unless the individual being screened understands what is known about PSA screening and makes the personal decision that even a small possibility of benefit outweighs the known risk of harms.”

USPSTF Co-Chair Michael LeFevre, M.D., M.S.P.H.
May 22, 2012

There’s no denying the potential “harms” that come with PSA testing. If the test is positive, chances are a biopsy will be ordered. If the biopsy is positive (as evaluated by something called the Gleason score, which I’ll talk about in another piece), chances are some kind of treatment will be recommended. And treatment, whether surgery or radioactive seed implantation, is not without consequences. But the alternative, including 28,170 expected deaths for the year 2012, is not preferable.

The Evidence Regarding PSA Testing and Prostate Cancer Treatment

First, let’s look at the evidence marshaled by the USPSTF in their full report. The basis for their recommendation was that although “screening based on PSA identifies additional prostate cancers, most trials found no statistically-significant effect on prostate cancer-specific mortality.” The report cites two trials to answer the question whether PSA screening decreases prostate cancer mortality, both of these described as being of “fair quality.” One of these, conducted in the US, followed 76,693 men for 7 years and found no significant difference between men assigned to PSA screening and those assigned to “usual care,” meaning no screening. However, it turns out that of the men in the usual care group, 44% had had a PSA test before entering the trial, and 52% had a PSA test at some point during the trial. That’s what you would call a thoroughly tainted control group. So they were basically comparing men who were supposed to have had PSA tests with men who were not supposed to have PSA tests, but many or most of whom had PSA tests anyway.

The other trial, a multicenter European trial, found that PSA screening every 2 to 7 years was associated with a 20% relative risk reduction in a subgroup of 162,243 men aged 55 to 69 years.

That’s not nothing.

However, there’s more. One of the participating centers, in Sweden, decided to publish their results separately. PSA screening every two years in a group of 20,000 men resulted in a decreased relative risk for prostate cancer mortality of 44% after 14 years of follow-up. That’s quite a lot more than nothing.

From my perspective, trying to trace the link between PSA-based screening and ultimate prostate cancer mortality or survival leaves out way too many intervening steps. The studies cited by the USPSTF used a number of cut-points for the PSA test, ranging from a low of 2.5 ng/mL to a high of 10.0 ng/mL, to determine the need for further evaluation, meaning needle biopsy. The studies all found that screening led to increased “incidence of prostate cancer,” meaning that more cancers were diagnosed, no surprise. But what then? What factors guide the decision on whether to treat, and what form of treatment? The USPSTF report is silent on this.

However, their review of data from studies comparing prostatectomy with watchful waiting found that prostatectomy was associated with “a sustained decrease in risk for prostate cancer-specific mortality (15% vs 21%, RR 0.62 [CI 0.44 to 0.87].” That means that men who opted for watchful waiting had about one-and-a-half times greater risk of death from prostate cancer than men who had prostatectomies. There was also a 25% lower risk for all-cause mortality, and among men less than 65 years of age, the relative risk reduction was 51% for prostate cancer mortality and 48% for all-cause mortality. The report also cites 8 cohort studies that consistently found prostatectomy associated with lower all-cause mortality (54% lower risk) and prostate-cancer mortality (68% lower risk).

At this point, my eyes are bugging out. How do you get to the point of deciding on a prostatectomy without previously having arrived at the diagnosis? How do you achieve that considerably lower risk of prostate-cancer mortality without previously having done the PSA screening?

The USPSTF did not take into consideration the very strong association between a man’s initial PSA score and his risk of death from prostate cancer. If a man’s first PSA score is between 4.0 and 9.9, his risk of death from prostate cancer is three times higher than that in a man whose first PSA score was less than 2.5. And if the first PSA score was 10.0 or higher, the risk of death is eleven times higher. This study, from the Duke University Prostate Center points to the desirability of starting to track the PSA score earlier in life, so that men with rapidly rising PSA scores can be identified. One fundamental anti-PSA-testing argument is that it is difficult to distinguish aggressive from indolent prostate cancer, but the association between the first PSA score and prostate cancer death strongly suggests that rapid increases in the PSA point to aggressive cancers.

In other words, the best practice may well be, start getting your PSA tested earlier, establish a baseline, and then monitor it. Not to do that seems to me to mimic the ostrich strategy for avoiding trouble.

And by the way, it’s worth noting that while the overall incidence of prostate cancer in the US is flat, the mortality rate is steadily declining – at about 3.9% per year, according to the CDC. To what might we attribute that? To watchful waiting?

I doubt it.

In short, we have to give the USPSTF credit for honestly reporting all the data that shoots their conclusion full of holes. Maybe they figured that it would be enough to release their recommendations to the media (as they did with their recommendations regarding mammograms) and hope that nobody would bother to read the fine print.

Finally, a paper in the journal Cancer published in August of 2012 reported that the incidence of metastatic prostate cancer on presentation would triple, from the current rate of 8000 cases per year, to an estimated 25000 cases per year if men did not get PSA tests. They did this by comparing the mean annual incidence of metastatic cancer in the last years before PSA testing became widespread (1983 – 1985) with the incidence rate in the most recent year for which there were data.

By the way, according to SEER, for the 93% of cases detected where the cancer is localized or regional, the 5-year survival rate is 100%, whereas for the 4% with metastasized cancer at diagnosis, it’s 27.9%.

I think those papers definitively discredit the USPSTFs anti-PSA test stance. You’d think they were trying to launch a job-creation program for undertakers.

* * * * * * *

As I said in my previous piece, I’m not a doctor, and I wouldn’t presume to give medical advice. My qualifications for scrutinizing and evaluating the pronouncements of organizations, whether government, academic, Big Pharma, or alternative health care, consist of a pretty good scientific background and a deep-dyed cussedness of character that disposes me to pick things up and look at their undersides. I look forward to your comments on this piece, and I’ll try to answer questions and say more about the current state of cancer treatment in a future piece.

Michael Jorrin (aka Doc Gumshoe)


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Leo
Irregular
Leo
June 1, 2013 12:25 pm

I am an 80 year old in good health and give much credit to the same attitude that Gumshoe has of looking under all the rocks. Many thanks to the members of the medical profession who respected their oaths (first do no HARM) and participated in these discussions. We need more participation. Miss Charlotte Truesdale brought tears to my eyes. Thanks Gumshoe.

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wes R
wes R
June 1, 2013 3:16 pm

There is a new test for breast cancer being rolled out that detects as few as 10 cancer cells. The breast is aspirated for a small amount of fluid and a test is run to detect cancer cells. 10 cell detection versus multi millions to be detected by mammograms and no radiation. http://www.atossagenetics.com

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Barry T
Member
Barry T
June 1, 2013 4:49 pm

I did not see any references to the PSA velocity or the “Free PSA” test. My very recent experience involved both. After a spike in my PSA count a couple of years ago I had a biopsy that turned out negative. As a follow up I visit my urologist every year at the 6-month point between my annual physical (which includes a PSA test). He noted from my annual physical 6 months previously, that my PSA count had increased over the year before and he did another PSA test. That test showed that the PSA level had doubled in the intervening 6 months. He referred to it as PSA velocity – the faster it increases, the more likely it is that something is awry. He then did another test for “Free PSA”. Just another finger full of blood to do the test. Based on the percentage of free PSA there is a look-up table to estimate the probability that cancer is present. I seem to recall that at a free PSA percentage of 25%, I had a 56% probability of having prostate cancer. The next step was a saturation biopsy of the prostate. Two tumors were found. The Gleason score was a 6. After discussions with the urologist, a surgeon and a radiation oncologist I opted for radiation therapy. After 4 weeks (and 5 more weeks to go) I feel no side-effects. I do feel relieved that the cancer was found and that I am receiving treatment and the prognosis is excellent. Prostate cancer is typically slow growing but in my case I went from being negative to a Gleason 6 in 2.5 years. I don’t know how typical that is…. anyone any idea?

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D. McCullam
Irregular
June 1, 2013 4:58 pm

Sounds like a moot issue. Medicare stopped paying my urologist for a post-surgery PSA over a year ago and he stopped submitting that charge to me or them(April. 2013). Pre surgery I would have paid for an annual PSA fee if the Fed were to renege, yet again. It was always accompanied by a digital exam which trumped the PSA.

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Patsy Robinson
Irregular
Patsy Robinson
June 4, 2013 5:35 pm

All these cost/benefit analyses do not seem to include the cost of the death of the patient, especially one that is still of working age. That person, if employed, pays income, social security and medicare taxes. Any minor or disabled children would be entitled to social security survivors benefits. Sometimes the spouse also would be eligible. The opposite might be true for the retired by the savings on Social Security, but many elderly are paying taxes on their retirement/investment income and that would need to be factored in. Are actuaries too expensive for these studies or are we just not interested in the social costs?

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Stephen Hamilton
Member
Stephen Hamilton
June 6, 2013 8:20 pm

In view of our FDA There is a bill going forward to allow new treatments for termanal cancer to allow new drugs and treatment with out all the FDA hoops. Also i feel that the pharamasutical buraucrats do not want to have a cure. unfortionatly there is too much to gain and they do not realy care about you

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Fred Doe
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Fred Doe
June 13, 2013 11:02 pm