What if the screening test hurt more people than the cancer?
Every so often I get an e-mail forwarded to me recounting the story of a friend or acquaintance recently diagnosed with ovarian cancer. The cancer is almost always far advanced, and the prognosis is very grim.
The e-mail reveals that the cancer might have been diagnosed much earlier if only the woman had been given a simple blood test (CA125 test) or had an ultrasound. Readers are exhorted to press their doctors for both tests, so that if they develop ovarian cancer, it can be diagnosed early, when treatment is more likely to be successful. The e-mail makes it sound like the means of diagnosing ovarian cancer is here, but doctors are ignoring the possibilities.
The situation is far more complicated. Yes, a simple blood test or an ultrasound can lead to early detection of ovarian cancer. Unfortunately, though, it also leads to tremendous numbers of unnecessary surgeries and the complications that result. In fact, it is entirely possible that screening for ovarian cancer is more dangerous than not screening for ovarian cancer.
That is the central message of a new study published today in Lancet Oncology, Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer. You might not realize that if you read newspaper accounts of the study, which emphasize the number of cancers diagnosed. Many newspaper accounts don’t mention that for every woman diagnosed with ovarian cancer, many more had unnecessary major surgery and quite a few suffered serious complications as a result.
The study screened more than 100,000 postmenopausal women for ovarian cancer. Half had ultrasound and CA125 tests (multimodal screening); the other half had ultrasound alone. Ovarian cancer was detected in 87 women, 42 in the multimodal group and 45 in the ultrasound alone group. That sounds pretty good until you learn that in order to make those diagnoses, 942 women had surgery. In other words, 855 women had major abdominal surgery for no reason. Of those, 24 experienced major complications including perforation of an organ (requiring surgery for repair), hemorrhage, deep vein thrombosis, and pulmonary embolus.
There was a big difference in unnecessary surgery between the multimodal group and the ultrasound group. Of the 942 women who had surgery, 845 were from the ultrasound group. In other words, adding the CA125 blood test made the screening more accurate. Even so, for every woman in the multimodal group who had ovarian cancer, 2 additional women had surgery that they did not need. In the ultrasound group, for every case of ovarian cancer diagnosed, approximately 19 women underwent major abdominal surgery that was unnecessary.
Screening hurt far more women than were helped. For every woman who was diagnosed with ovarian cancer, 9 more had surgery that they didn’t need, and 2.8% of women who had unnecessary surgery sustained serious, life threatening surgical complications. That is a pretty dismal record for a screening test.
If we leave aside the ultrasound only group, the results in the multimodal group are far more encouraging. Only 97 underwent surgery, of whom 42 had ovarian cancer. As mentioned above, for every case of ovarian cancer diagnosed in the multimodal group, 1 woman had surgery that she didn’t need. Of those women who had unnecessary surgery, 4.2% sustained serious, life threatening complications.
What would happen if we instituted multimodal screening for all post menopausal women. For every 1 million women screened, 866 cases of ovarian cancer would be diagnosed, 1034 women would have unnecessary major abdominal surgery, of which 43 would sustain major, life threatening complications.
In addition, we do not know if the early diagnosis of ovarian cancer in these patients would improve outcome. Over half of the women diagnosed by screening already had advanced disease, so it is unlikely that screening improved their prognosis. Moreover, even early stage ovarian cancer is a dangerous disease, and many of these women are going to die anyway.
The ultimate value of a screening test is in lives saved, and that information is beyond the scope of this study. It is already clear, though, that for every life saved, 4 or more women will have unnecessary major abdominal surgery, some women will sustain life threatening complications, and inevitably, some women will die from complications of surgery that they did not need.
This study is large, comprehensive and well done, but it does not support mandatory screening for ovarian cancer. It demonstrates that large-scale screening is possible, and that early ovarian cancer can be diagnosed by screening. Unfortunately, it also shows that large-scale screening efforts results in substantial harm to more people than are helped. When the screening test is potentially more dangerous than the disease, it makes no sense to implement mandatory screening.
TIP:
Enter the amount, and click "Tip" to submit!
MissingK8
aliquot
Roger Fallihee
madcelt
Norwonk
John Moore
Salon.com
Comments
"The media rarely report the negatives about cancer screening."
That's usually because they take their information directly from the press release put out by the authors. They really should read the paper (and other papers in the field) in order to determine whether the press release accurately portrays the results.
To read the news articles, you'd think that ultrasound or ultrasound plus CA125 are new ways of screening for ovarian cancer. They're not. Similar studies were performed more than 2o years ago and the results were the same: the risks of screening outweigh the benefits.
The key feature of this study is that it is large, comprehensive and done well. However, it doesn't show anything different from previous studies. There has been no discovery of a new screening test for ovarian cancer. There has only been confirmation that previous screening tests still aren't safe enough to put into use.
Rather than saying, "Let's get rid of the blood tests and ultrasounds," couldn't we be focusing our efforts on cutting back on the invasive procedures doctors are doing subsequently? If 90% of women who tested positive with the non-invasive procedures didn't really have cancer, it seems to me the problem is with the non-invasive procedures.
Wrong 90% of the time isn't good odds!
As for any "old boys network" regarding disease treatment, that's missing the point. It's not some sexist/racist conspiracy, it's the inevitable consequence of the free market combined with non-socialized medicine and lobbying being completely legal. Those whose diseases are profitable to treat are obviously going to get the most spent on research into those diseases. It's not pretty, but it's not a conspiracy.
"Seems to me, that if men contracted ovarian cancer, it would have been studied much earlier with much more money behind it."
That's simply not true. The cancer that receives the most research dollars and attention is breast cancer, even though there are other cancers that kill far more people.
Ovarian cancer is dangerous for the same reason that pancreatic cancer is dangerous. Both are located deep within the body. Both can grow and metastasize without initially causing symptoms. Therefore both are not usually diagnosed until they are far advanced and very difficult to treat successfully.
The reason that cancer has not been cured yet is not for lack of money or desire. It is a very complicated disease, and almost certainly has a genetic component. As our knowledge of cancer biology and our knowledge of the genome increases, the cause and cure of cancer will come into view.
Cancer is still a terrible disease, but we have made substantial progress. When I was in medical school, the only options we could offer cancer patients were to poison them (chemo), burn them (radiation) or cut them (surgery). Those are still the mainstays of cancer treatment, but in recent years highly effective, targeted, non-toxic treatments like Herceptin and Gleevec have been developed. Such treatments represent the future of cancer treatment, and many people are working very diligently to improve cancer care.
"Rather than saying, "Let's get rid of the blood tests and ultrasounds," couldn't we be focusing our efforts on cutting back on the invasive procedures doctors are doing subsequently? If 90% of women who tested positive with the non-invasive procedures didn't really have cancer, it seems to me the problem is with the non-invasive procedures."
This is the fundamental difficulty in designing ALL screening tests. Every screening test has a false positive rate and a false negative rate. In the case of the ovarian cancer screening test, the false positive rate is the percentage of women identified as having cancer who don't have cancer; the false negative rate is the percentage of women identified as healthy who actually have cancer.
Here's the most important thing to keep in mind: the false positive rate cannot be lowered without raising the false negative rate. In other words, when the standards for screening are tightened so that there will be fewer false positives (fewer unnecessary surgeries), the false negative rate will go up. In other words, in exchange for decreasing the unnecessary surgeries, some cases of ovarian cancer will be missed.
In general, in order to be effective, a screening test must have a very low rate of false negatives. It can't miss may cancers or it is useless. Unfortunately, in the case of CA125 and ultrasound, setting standards that will pick up most cases of cancer also result in lots of false negatives. That's not surprising when you consider that there are many other reasons for elevated CA125 or abnormal ultrasounds besides ovarian cancer. For example, elevated CA125 is found in endometriosis. So although every woman with ovarian cancer has elevated CA125, most women with elevated CA125 don't have ovarian cancer.
The holy grail of ovarian cancer screening is to find a substance that is produced by the cancer and only by the cancer. To date, no such substance has been identified.
The important point is that researchers are well aware that this type of screening has a very high false positive rate. There's just nothing better out there at the moment.
Empirical medical science has its strengths and weaknesses, but most of its practitioners don't seem to want to admit the latter.
Or is he or she saying, "Your initial screening tests shows that you have cancer and we'd like to do another screening test to confirm it"?
The difference strikes me as pretty important.
"Isn't this just par for the course with empirical medical science? "
Do you mean the fact that medicine is not perfect? Do you mean that tests and treatments have side effects? Or do you mean that governments and people spend millions of dollars and countless hours carefully trying to determine the best ways to diagnose and treat cancer? Perhaps you mean that medical scientists publish their research in peer review journals so other people can analyze it and point out its defects?
Medicine is indeed imperfect, but it is certainly a hell of a lot better than any alternative. None of them cure anything. None of them research side effects. None of them research effectiveness. None of them publish peer review investigations that can be read and analyzed by all. In fact none of them even comes close on any measure of anything except that alternative medicine is much more likely to con the gullible.
I wasn't making an argument for the validity of alternative medicine, and if I were I wouldn't bother debating it with you, because I don't see any willingness to challenge your own preconceived notions. I am open to the possibility that I am mistaken in this perception.
And of course even a child knows nothing is perfect. I just have a very clear understanding of the philosophical and methodological flaws of any empirical and/or scientific exploration. I'm also clear on the strengths, a point which was quite explicit in my comment.
I have been harmed by the arrogance of doctors, as have many people I know. I've also met some doctors that aren't like that, and even those have admitted that most doctors are indeed arrogant.
I don't know how much more neutral I can be in a comment than this, but if you assume and project and twist it into something it is not, then that is your choice and your right.
"I have been harmed by the arrogance of doctors, as have many people I know. I've also met some doctors that aren't like that, and even those have admitted that most doctors are indeed arrogant."
What does that have to do with this discussion? We are talking about the results of a scientific study that has been presented in a peer review journal for everyone to analyze.
The fact that this particular screening test has a very high false positive rate has nothing to do with anyone's personality, let alone their arrogance. It is an empirical fact, derived from conscientious, high quality scientific study.
Designing an effective screening test is always difficult primarily for the reason I mentioned above. Every time you lower the false positive rate, you raise the false negative rate. That is a law of probability and there's nothing anyone can do to change it.
When I spoke of the arrogance of doctors, I was referring to my original statement: "Empirical medical science has its strengths and weaknesses, but most of its practitioners don't seem to want to admit the latter." My point is that , in general, medical professionals don't like to acknowledge the weaknesses because they are arrogant, and this is comparable to the intellectual arrogance of most scientists and empiricists. The scientists I most admire are those who are capable of maintaining some humility and a balanced perspective while also questioning the dominant paradigms in their field. Their investigations and results are the stronger for it.
I have been told that sometimes I come across as hostile when I think I am being neutral. I did not intend hostility, but it does bother me when any attempt, judicious or not, to critique the beliefs and practices of medical science is automatically interpreted as some kind of naive gullibility. That smacks of pure arrogance to me. And arrogance causes great harm in this world, in so many many ways.
"Breast Cancer has more money spent on it NOW and the past decade because of the Women's movement of the 1970's and the many women that are now at NIH and other research institutions."
That's not true, either.
First of all, women have their own medical specialty (OB-GYN) and men have nothing comparable. Second, it is simply bizarre to suggest that scientists think men's cancers are more important than women's cancers. Just as you have been profoundly affected by your mother-in-law's experience, men are equally affected by the illness and deaths of wives, mothers and daughters.
The emphasis on breast cancer research had nothing to do with feminism or the number of women in medicine. It is the result of the activism of the gay community on the issue of AIDS. The changes that they wrought in the system made it much easier for consumer groups to exert pressure. That's why funding for both AIDS and breast cancer are completely out of line with their actual impact. AIDS activists and breast cancer activists have commandeered an unfair share of research money far out of proportion to the actual impact of the diseases.
I have written quite extensively about the problems in medicine, including the arrogance of doctors, but that is not what is going on here. It has nothing to do with this issue.
"if men had ovaries (they do have testicles and prostate glands), we would have found a more reliable and less expensive (and, yes, now that we have micro-surgery, less invasive) ways of detecting ovarian cancer"
You mean like the PSA test which has led to approximately 40% of men being over treated for cancers that would never have harmed them. You mean like prostatectomy, the treatment for prostate cancer, that leaves men impotent and infertile.
Yeah, right. They've certainly figure out how to make it easy for men.
"The Skeptical OB is fine spelled out but the logo up top looks like initials."
Thanks, but that's deliberate.
As her daughter, I insist on an annual CA125. If it's ever elevated, I'll be very cautious regarding how I proceed from there.....ultrasound & second opinions would be my first step. But frankly, if all pointed to OvCA, I'd get the surgery. I'm well aware that CA125 can be elevated for other, far more benign conditions. Some of those could be ruled out just by history & testing. Others might not be ruled out until surgery -- I'd be willing to make an educated decision at that point and would like the decision to be MINE based on good testing & the best advice I could obtain.
Mom had good docs, and one did tell us about genetic testing, specifically for BRCA1 or BRCA2. My own research resulted in understanding the need for testing for these genetic mutations and, if necessary, prophylactic oophorectomy & removal of fallopian tubes. This was fairly far into the process, though, and she had a wonderful oncologist with whom I developed a good working relationship -- he told me about this during one of our many meetings. I have to wonder how many women aren't given this information.
I actually considered having the prophylactic surgery anyway. Although it's a drastic measure, I don't see it as radically different than the women who have genetic loadings for breast cancer & get prophylactic mastectomies. Without the presence of genetic mutations indicating a higher risk, though, I determined it wasn't necessary.
"I have to believe that if my mother had a simple CA125 & ultrasound when she started complaining about symptoms 2 YEARS before she was ultimately diagnosed with OvCA, she MIGHT still be alive."
You are probably right. The situation is entirely different when someone develops symptoms. In that case, both ultrasound and CA125 may be warranted in an effort to diagnose the ongoing problem.
In fact, any woman who experiences symptoms like abdominal bloating, abdominal or pelvic pain, difficulty eating or feeling full quickly, lasting more than 2-3 weeks should see a doctor. If the symptoms persist, she should insist upon both an ultrasound and CA125.