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The American Cancer Society

The Overdiagnosis of Prostate Cancer: Is It News?

by Dr. Len March 10, 2009

An article and editorial in today’s edition of the Journal of the National Cancer Institute about prostate cancer screening highlight the differences between the messages of science and the expectations of the media and the public, and how the two intersect.

 

The end result is that the science message from the article may be converted into a bit more sensational story than suggested by the conclusions of the research.  After all, talking about science simply isn’t sexy.  Talking about how medical tests harm patients is a surefire way to capture the attention of the public.

 

The research, which is interesting and well done from a science point of view, deals with the difficulty we have getting our arms around the fundamental question of how many prostate cancers are diagnosed by screening for the disease  to find it early that would otherwise not cause a man harm or death.  This is what doctors call “over diagnosis.”

 

The paper starts out by noting that previous studies claim the over diagnosis rate for prostate cancer—which is the percentage of prostate cancers diagnosed that never would have been a problem for a man—has ranged from 25% to over 80% of cancers diagnosed by prostate cancer screening.  That is a lot of men who apparently have no benefit from having been diagnosed with this disease.

 

The researchers then took a more careful look at the question of what the real number should be, by using different complex mathematical models and standardizing various definitions as part of the study.  They found that from 42% to 66% of prostate cancers were “over diagnosed.” 

 

The other interesting observation was that these cancers were diagnosed from 6.9 to 7.9 years earlier than would have been the case without screening.  This is what we call “lead time bias.”

 

The conclusion?  According to authors, “The precise definition and the population used to estimate lead time and over diagnosis can be important.”

 

The authors go on to say, “ The lead time and the likelihood of over diagnosis are quantities that are critical in the assessment of the likely benefits and costs of any screening test; yet, in the case of PSA screening, results have been variable and confusing. This article is the first, to our knowledge, to closely examine the reasons for discrepancies across studies. Our results clearly show that the context or population used to derive the estimates, the definition of lead time used, and the estimation methodology all have important roles.”

 

Now, I am not saying that this research isn’t good work.  It is, and it is important work.  But it is important to scientists who study this problem, and probably not very interesting to most of the lay public.

 

The editorial which accompanied the article did in fact go on to relate the study itself to the questions surrounding the impact of prostate cancer screening. 

 

The editorialist concluded—as does the American Cancer Society—that we really aren’t certain how many men we are helping by screening for this cancer.  Until the evidence is in, both the editorial and the American Cancer Society along with a number of other highly regarded professional and science-based organizations recommend that men review the pros and cons of prostate cancer screening with their doctors.

 

This question is important, because since the advent of prostate specific antigen testing (PSA) in the late 1980’s, there has been a considerable spike in the number of men diagnosed with prostate cancer.  There was also an initial surge in deaths from prostate cancer in the United States after we began using the PSA test, followed by a substantial decline in prostate cancer deaths in this country that continues through the present day.

 

The problem is that we can’t specifically tie the two events together in a cause and effect relationship.   The same trends have been seen in other countries that do not regularly screen for prostate cancer.  There are also discrepancies here in the United States when you compare areas where men are regularly screened for prostate cancer and other areas where they are not.  Death rates have been dropping under both scenarios.

 

In the meantime, long term (and I mean long term) clinical trials to find out whether or not screening for prostate cancer saves lives have been ongoing in the United States and Europe, and we are still awaiting the results.

 

On top of this dilemma we have the fact that we are ramping up the war against prostate cancer.  We are employing new surgical techniques such as robotic surgery and engaging proton beams to treat the disease.  These approaches may be saving lives, but we don’t know for certain which man actually benefits from these treatments.  And they come at a not insignificant financial and personal cost.

 

Inevitably, as you treat a man for prostate cancer—especially an older gentleman who may have other significant medical condition—you run into situations that are not pleasant.  Pain, bleeding, incontinence, and impotence are not uncommon.  Surgical deaths do occur. 

 

When we screen for a particular cancer, we want to know that we are helping more than hurting.  We call this the “benefit vs. risk” ratio.  When the benefits outweigh the risks, it’s a good thing because we save lives.  Screening for breast, colorectal and cervical cancers on a routine basis are examples of effective use of screening.

 

On the other hand, if we hurt more than we help when we screen for a particular cancer, it is not a good thing.  Prior studies suggested that was the case for lung cancer.  Newer clinical trials are underway using CT scans to find out whether our current technology may improve that situation.

 

Prostate cancer screening may fall somewhere in between.  There are strong voices on both sides of the argument whether or not prostate cancer screening works.  That’s why the American Cancer Society recommends you have an informed conversation with your health care clinician before embarking on a course of routine annual screening with the PSA test and a rectal exam to look for prostate cancer.

 

Another factor we consider when making a screening recommendation is how many people will we treat where it wouldn’t have made a difference?

 

That may sound strange to some, because it is the commonly held belief that every cancer is a bad cancer that will cause harm.  But that’s not quite true.

 

We have known for decades that there are several different types of cancers that may exist in our bodies but never become apparent to us or our doctors. 

 

For example, we know that many people have thyroid cancer that in the past would never have been diagnosed and never caused harm.  Now, with our newer methods to look at the thyroid gland, we are finding many more cancers.  We may be diagnosing more thyroid cancer on a population basis because we can find them, but it isn’t clear that there are in fact more thyroid cancers being found that would have led to serious medical consequences if they had never been discovered in the first place.

 

We have also known for decades that prostate cancer was close to universal in men who approached the century mark in their lives.  But those cancers were found incidentally at autopsy, and never caused a problem.  Even men like me (I am not going to reveal my age here, but my hair is a bit gray) have a fairly high percentage of prostate cancer that would be found if one decided to go looking for it, even with a very normal PSA test.

 

So here we are on the horns of the dilemma which I mentioned earlier in this blog.

 

There are many, many men out there who firmly believe that prostate cancer screening saved their lives.  There are many expert physicians who agree with them. There are many expert physicians who do not agree.

 

There are many hospitals and community organizations that regularly run “prostate cancer screening fairs” as a means of finding men with this cancer (who then go on to spend thousands of dollars at the hospital and/or the medical practice or elsewhere when they receive treatment for their prostate cancer).

 

But here is what we know and have known for some time:

 

We test a lot of men for prostate cancer.  We find a lot of men with prostate cancer.  There are many men we treat who probably would have been fine without finding their prostate cancer.  There are many men we treat where our treatment didn’t make any difference, and they would have died from their prostate cancer no matter when we diagnosed it or how we treated it.  There are some men we treat where finding the cancer through screening probably did save their lives.  And for many of the men in each of these groups, we have changed the quality of their lives forever and not necessarily for the better.

 

The problem is we don’t know which men belong in which category.

 

So I come back to my initial thought: here is a well done research study published by reputable investigators in a reputable scientific journal that makes a legitimate scientific point.  And the editorial expounds appropriately on the implications of the research relative to the impact of prostate cancer screening.

 

That’s important, but it isn’t really news to many of us familiar with this issue.

 

I suspect you will be hearing about this story and its implications in an entirely different context, and probably in a way that will cause you concern and lead you to ask questions that really in fact are not related to the primary purpose of the research.  In fact, the reports may actually frighten many of you.

 

Hopefully the news stories will lead you or someone you love to have a better understanding of the controversy surrounding the “early” diagnosis of prostate cancer.  Hopefully that will lead you to have an honest discussion with your doctor.  Hopefully you will become more informed about this aspect of your health care.  Someone who is informed about their health will likely be someone in better health.

 

Maybe that isn’t such a bad thing after all. 

Comments

3/12/2009 12:24:40 AM #

Ron Bucher

Articles like the one written by Lauran Neergard (which quoted Dr. Lichtenfield) are a great disservice to men and the doctors who treat prostate cancer.

I was diagnosed "early" with prostate cancer at age 54. Elevated PSA was my ONLY symptom. Prostate cancer starts in the middle of the prostate and grows outward. Mine had reached the capsule, and had advanced far enough that surgery would not have been an option if it had advanced further.

After my surgery, I shared a hospital room with another man about my age who also had prostate cancer. Unfortunately his was diagnosed too late and had spread to his colon. He was in extremely bad shape and might not be alive today.

There is no doubt that PSA testing saved my life. So when I see these articles criticizing PSA testing it makes me very sad for all the men who will die (and their families and friends) because they were discouraged from PSA testing.

Ron Bucher

3/12/2009 9:22:03 AM #

Jud Pratt

We have a business plan, about to be funded,for an exam glove with an embedded sensor that measures the volume of the prostate during standard prostate exam in the doctor's office.It's primary use is for diagnosis and treatment of BOO (size,velocity, and acceleration); a side benefit allows calculation of PSA Density. This could help reduce unecessary needle biopsies by identifying men whose PSA is elevated due to prostate enlargemnt alone.

Jud Pratt

3/12/2009 9:33:38 AM #

Len Lichtenfeld

Ron, I appreciate your comments.  If you read the blog carefully, you will note my comment that we may be helping some patients with PSA testing, harming some patients through treatment that might otherwise not have had an impact on their disease, and subjected others to treatment they may not have needed.  The unfortunate reality, as I wrote, was that we can't tell which men fall into which category.

One of the issues that I do believe we need to answer is whether PSA testing is more valuable in certain age groups, such as a younger man like yourself.  There is probably an increased incidence of prostate cancer diagoses among men in their 50's than was the case in the past.  Whether that translates into improved survival or simply earlier diagnosis (lead time bias) isn't certain, but needs to be addressed.  I am familiar with many cases like yours, including people I know personally. But what we don't have at this point is the scientific data to answer the question whether it truly makes a difference among the larger population of men.

As noted in the blog and by many others, we need the results of the clinical trials that are currently underway.  Hopefully they will be available soon, and help guide us to better understand the value of PSA testing.

In the meantime, the American Cancer Society recommends that men have a careful discussion regarding the potential benefits, risks and harms of PSA testing so they make an intelligent, informed decision.  That statement doesn't mean should be tested or shouldn't be tested with PSA.  It does mean they should have an understanding of the issues so they can make the best decision for themselves.

Len Lichtenfeld

3/12/2009 11:59:24 AM #

Gregory D. Pawelski

Prostate cancer is an unpredictable, stochastic, evolutionary process. It is unknowable if early-stage prostate cancer will progress and cause clinical disease in a given patient. I would want to see results of a prospective, randomized trial showing actual survival advantages (as well as a comparison of the cost in terms of treatment associated morbidity) before subjecting myself to the PSA test and the possibility of then getting directed to biopsies and then getting directed to radical prostatectomy without any clear indication that this was in my advantage.

Gregory D. Pawelski

3/12/2009 2:05:40 PM #

Rob Addias

We’re using what to me sounds like weak screening methods that seem to result in more people being over treated then the number of people whose lives are extended. Sure, some lives are being prolonged but at what cost to the lives of those who are over treated, some at great risk, discomfort, anxiety, disfiguration and lower quality of life.

We have the PSA and CA125 blood tests. Both of those have problems of specificity. There have been various controversies surrounding mammograms ranging from x-ray exposure to too much compression to what a “normal” image should look, false positives and false negatives. At what age to start screenings and how often.  Should DCIS be treated or watched or what?

Colonoscopy has risks such as bowl prep problems, perforation, anesthesia complications (anesthesia for a screening procedure?!). Does colonoscopy do a good job of detecting cancer in the right colon?  Where in the colon do most colon cancers occur?

My wife had a palpable breast lump. The mammogram couldn’t tell us anything other than there was a lump. Beautiful! The ultrasound, fine needle biopsy and the way it palpated all indicated it was benign.  No family history and no other risk factors.  But the doctor wanted it out in case it might turn into cancer!  But wait, I thought that doesn’t happen.  Benign stays benign, right? Post surgical pathology indicated again; benign.  Over treatment and, I believe misinformed consent.

My dad’s first colonoscopy found a suspicious flat growth that was too risky to remove endoscopically.  The doctor recommended surgery without any proof of cancer.  Dad refused.  Another scoping 5 years later and he’s OK. Potential over treatment avoided!

We need real screening tests that work.  And we need a system where doctors aren’t afraid of being sued.  Ah yes, could law be playing a roll?

Why is it so hard to replace the established methodologies?  It seems that any proposed new test must clear a hurdle much higher than the hurdle cleared by the established tests. Could it be that there is too much vested interest (money) surrounding current methods?  But we can incrementally “improve” current screening without any hurdles it seems.  As an example, mammography went from analog to digital and then we added computer aided detection.   Did any of those alleged improvements get subjected to very much scientific scrutiny?  Was digital mammography proven to increase detection of actual cancers and reduce false pos and neg results?  Or was it mostly just accepted as “if it’s digital it must be better”?

And how about more research and education into the prevention of cancer.  Maybe because there’s no money in that?  And then there’s the confusion created around what we think we know about prevention.  Coffee is bad.  No wait, it’s good.  Red wine is good.  No wait, it’s bad.  Exercise cuts your risk of cancer.   No wait, we’re not sure it makes any difference but we think it’s still good for you so keep doing it.  Vitamin D lowers your risk of cancer.  No wait, it’s just good for your bones.

More questions than answers, unfortunately.

Rob Addias

3/13/2009 10:38:03 AM #

John Marshall

I concur with comments by Ron Bucher, and the headline in my local paper did a further disservice to men.  I nearly died at the age of 50.  The cancer had well consumed my prostate and was on its way to other feeding grounds.  Apparently I had cancer since my late 20's according to my surgeon at the Henry Ford Medical Center in Detroit.  I had the robotic surgery and it saved my life. With a PSA earlier it may have left other things a little more intact.  Perhaps the term "over diagnosing" isn't quite correct because it brings RED into my eyes.  Maybe the term "over-treatment" might be a better way to describe the treatment of men in their late stages of their life.  And by the way, if Lycopene helped prevent cancer I would have never gotten it.  I eat tomatoes like it's my job.

John Marshall

3/16/2009 5:45:17 PM #

Thomas Thompson

I am eighty-eight years old. My prostate cancer was diagnosed when I was seventy-four years old.  I deemed that all my options were of a "temporary" nature. My PSA was 6.8 and on the Gleason scale5.  I opted for the Orcheichtomi. My PSA went down near 1.0 very quickly.  Today, fifteen years later my PSA it is 0.4. I live in a single family home with all the maintenance duties.  My worry is that I will lose my driving priveleges when I am ninty.

I have a friend who was diagnosed with prostate cancer at the same year.  He opted for the "temorary" therapy as in hormon therapy. He is now enduring skelatol pain. He must live in an assisted living facility as a result.  He is not likely to die of something else.  

Screening should be a vital part of health mainenance regiman.

Thomas Thompson

3/16/2009 5:55:34 PM #

Thomas Thompson

I have a colonoscopy every five years.  Two or three precancerous polups are removed each time. I am eight-eight years old. The screening is a vital part of my longevity.
I have a friend how died at 60 of colon cancer.  Doctors found the colon cancer when looking into his mouth where a sore was bothering him.  THEN he had a colonoscopy.  His cancer had metatasized to other parts of his body.

Please note that screening saves lives.  It should be a part of your health maintenance regimen.

Thomas Thompson

3/17/2009 7:53:52 AM #

Kathy

Ultimately,  every case of prostate cancer today was found via psa and dre SCREENING and the PSA is not really the culprit in over diagnosis and treatment.......it is a useful tool that  in my opinion, that helps save lives.  We encourage men to know their PSA just like they would their Cholesterol.

In my mind the big problem is physician education and additional use of Active Surveillance for the men who are appropriate. We all know and you said that some men are saved because of screening therefore are we willing as a society to sacrifice these men because of harms that other men may experience when we should be working with the physician community to stop the rush to inappropriate treatment?

If all the money and time that is being spent on educational material about screening were spent on working on educating the physician community about who needs immediate treatment and who can wait and be monitored along with developing patient material about the realities of prostate cancer and who can avoid immediate treatment we would have a more balanced result that would help the men who are dealing with a diagnosis of prostate cancer?

The real issue is not to screen or not screen, the issue is to treat or not treat?

Kathy

3/17/2009 8:27:55 AM #

Roy Starrin

With the advent of universal health care, the "effectiveness"issue  will soon come that of what is cost effective. Then all us old coots will be permitted to die of benign neglect since there is no cost effect reason for us to live.  We've lived long enough. Please die and reduce health care costs.

Roy Starrin

3/17/2009 10:36:27 AM #

G. Hothersall

PSA Screeing saved my husband's life---Pca missed on 1st biopsy 6 yrs later it was found. Biopsy indicated an insiginficant indolent cancer we were told by local uro. Had my husband not had a ralp when he did ---and by a skilled experienced ralp surgeon ,  he may have not had clear surgical margins . Gleason up graded 3+4 and the cancer was EXTENSIVE---no that's one word one does not want to see in a path report! Other than thyroid disease he is in good health for mid sixties---no bp meds---only a natural dessicated thyroid pill.Until physicans can make the determination that a Pca found is either indolent or aggressive PSA screening should be done. Dosen't mammography cause unnecessary biopsies as well as other imaging to be preformed? Why not do RESEARCH to find screening tools for Pca that can make the determination wether you are delaing with a lion or lamb---also more accurate biopsies are needed.

G. Hothersall

3/17/2009 11:28:32 AM #

Charles (Chuck) Maack

My first PSA exam occurred when I was 59 years of age and resulted in a sonogram that only indicated BPH (obviously in error).  Later the same year a free screening resulted in my first DRE with the urologist suggesting I wait for the PSA result from this screening then see a urologist since the DRE determined nodule development.  PSA had increased to 6.8ng/ml.  Urologist recommended open surgery (December 1992) and pathology of removed gland found no extension of cancer to lymph nodes, seminal vesicles, or vas deferens, BUT, extesnion into "fatty tissue."  This resulted in EBRT.  Subsequent three years PSA <0.1ng/ml, then recurrence.  Now, over 16 years later, a continuing PC patient surviving with intermittent ADT.  Had PSA and DRE been recommended at earlier ages back then, my cancer could have been caught sufficiently early that most any treatment option would have eradicated the cancer.  I am a strong proponent for PSA and DRE examination beginning at 35 years of age for African Americans and men with a family history of PC or BC; 40 years of age for all others.  I meet too many men with already advanced disease in their early 40s.  We should have the right to know whether or not cancer is in the developing stage in our bodies.  The problem in "overtreatment" begins at the physician/urologist/radiation oncologist level.  These are the medical professionals who require direction in recommending when and when not to treat our insidious men's disease.  Yet, as patients and knowing we have a cancer developing, we, too, have the right to "treat."

Charles (Chuck) Maack

3/17/2009 3:47:31 PM #

Chris Faulk

Dx stage III with possible bladder involvement at age 49.  The AUA recommends PSA at age 50.  PCa has been around a very long time.  Enough of the controversy! I urge, beg and compel Medical "Science" to develop the tools to diagnose agressive cancers and treatments that minimize related morbidity.

Chris Faulk

3/18/2009 9:30:09 AM #

Rob Addias

I think the perceptions of current cancer screening tests come down to this:  People who were helped by a particular screening test, i.e. it found real cancer, believe the screening test was great and we should all take it.  People whose treatment turned out to be unnecessary and were harmed by that treatment want better screening tests.

Any screening method that produces false positive results and especially lots of false positives, will find cancer because it causes the physician to look more invasively for cancer.  If you look for cancer in enough people you will find it in some.  But is that really the definition of a good screening test?  And how does the physician know if the cancer indolent or not?

And let’s stop talking about the “perfect” screening test because perfection doesn’t exist anywhere in the real world, only good enough.  

What then, is “good enough”?  In my opinion any screening test would have to meet the following criteria to be good enough:
1.  Be specific in that it tells the physician where in the body the cancer is located.
2.  Is able to distinguish between indolent disease and disease that actually needs treatment.
3.  Accurate in that it produces “very small” numbers of false positive or negative results (how about 95% accurate).
4.  Has very low risk to the person to which it is administered.  In other words, test it against the “pregnant woman” hurdle.  If you can safely administer the screening test to a pregnant woman then it’s OK.  The benefit of that hurdle is that the screening test itself should not increase your risk of getting cancer in the future not even by a small amount.  Nor should the screening test subject the person to any amount of collateral risks associated with the performance of the screening procedure.  That will make it fair to the people whose individual risk of getting a particular cancer may actually be zero (I know that’s unknowable in practice).
5.  It isn’t so expensive that if we screen the entire target population (e.g. men or women 40 and up or 50 and up) it doesn’t bankrupt the health care system or occupy so many resources that it interferes with access to diagnostic care.

Rob Addias

3/18/2009 12:17:30 PM #

Gregory D. Pawelski

The goal of the federal investment in comparative effectiveness research is to provide clear information about the risks, benefits and costs of various treatments of specific diseases. Given the volume of misinformation already available in the health care arena, comparative effectiveness research would be extremely valuable.

-------

The funding doled out in the recent stimulus bill would focus on producing the best unbiased science possible. Comparative research has the potential to tell us which drugs and treatments are safe, and which ones work.

-------

This is not information that the private sector will generate on its own, or that the "industry" wants to share. Companies want to control the data, how it is reviewed, evaluated, and whether the public and government find out about it and use it. Just about the way they are controlling data now.

-------

Comparative effectiveness research is not something for patients to be afraid of. It can help doctors and patients, through research, studies and comparisions, understand which drugs, therapies and treatments work and which don't.

-------

Nothing in the legislation will have the government monitoring treatments in order to guide your doctor's decisions. Doctors will still have the ultimate decision, along with the patient.

Gregory D. Pawelski

3/18/2009 12:29:21 PM #

Gregory D. Pawelski

The goal of the federal investment in comparative effectiveness research is to provide clear information about the risks, benefits and costs of various treatments of specific diseases. Given the volume of misinformation already available in the health care arena, comparative effectiveness research would be extremely valuable.

-------

The funding doled out in the recent stimulus bill would focus on producing the best unbiased science possible. Comparative research has the potential to tell us which drugs and treatments are safe, and which ones work.

-------

This is not information that the private sector will generate on its own, or that the "industry" wants to share. Companies want to control the data, how it is reviewed, evaluated, and whether the public and government find out about it and use it. Just about the way they are controlling data now.

-------

Comparative effectiveness research is not something for patients to be afraid of. It can help doctors and patients, through research, studies and comparisions, understand which drugs, therapies and treatments work and which don't.

-------

Nothing in the legislation will have the government monitoring treatments in order to guide your doctor's decisions. Doctors will still have the ultimate decision, along with the patient.

Gregory D. Pawelski

3/18/2009 10:41:34 PM #

Bruce Nolan

I'm living with an enlarged prostate, have had quarterly PSA and 3 negative biopsies in the last  5 years. So this is impt. to me. But here's the thing, given so much continuing uncertainty out there, what are we supposed to discuss with our doctors? Presumably, they apprehend the ambiguity of all this even more than we do. So, absent clear warnings like family history, how could a doctor favor  treatment over "watchful waiting"?

Bruce Nolan

12/26/2009 1:12:25 AM #

Michael

I have been reading about a new Clarient Gene Expression Test for Prostate Cancer.  Is this test better or worse than the PSA test given now?

Michael

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About Dr. Len

Dr. Len

J. Leonard Lichtenfeld, MD, MACP - Dr. Lichtenfeld is Deputy Chief Medical Officer for the national office of the American Cancer Society.

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