Cancer Testing -- Fueling New Debate on Cancer Screening

[Guest guest]

I found this article in **2002** and included it in an alternative medicine

ezine in which I was co-editor. Amazing that this very information was

KNOWN in 2002 and in 2009 we still will not believe it.....

April 9, 2002

Test Proves Fruitless, Fueling New Debate on Cancer Screening

By GINA KOLATA

For years, it was a medical truism that the earlier cancer could be

detected, the better. Most cancers would inevitably worsen if left

untreated, the theory went. Spontaneous remissions were so rare as to be

almost unheard of.

But last week, those assumptions were shattered, at least in the case of a

childhood cancer. A screening test that looked as if it would save children

from terrible deaths from a cancer of the nervous system utterly failed to

fulfill its promise.

Now the story of that screening and questions about tests for adult cancers

like mammography and a blood test for prostate cancer are ushering in a

broader debate about cancer screening in general, with questions about what

is known of the benefits and risks of tests that look for cancers in healthy

people with no symptoms.

The questions are pressing, because cancer remains a leading killer. In

1998, the most recent year for which data are available, 541,519 Americans

died of cancer. Men have a 43 percent chance of developing cancer in their

lifetime and for women the lifetime risk is 38 percent.

And there are no easy answers. The recent mammography debates have led some

experts to suggest that women and their doctors study the issues and decide

for themselves, a course of action that others say is confusing.

But as the debate over mammography and over other tests, like the one for

prostate cancer, burn on, the childhood cancer test is giving some experts

pause.

The cancer was neuroblastoma, an attack on the nervous system that is one of

the most common, and most lethal, tumors in children. Researchers in Japan

had found that a urine test could find signs of the cancers long before

symptoms appeared.

A large screening program started in Japan, while studies of the test began

in Quebec and Germany. At first, the results looked spectacular. Many more

cancers were found, and they were found early. Children underwent surgery,

usually of the adrenal gland, where the tumors tend to lodge, and their

cancers went away.

But to the investigators' shock, there was no decline in the number of

toddlers who developed advanced cancers, and the death rates from the

disease stayed unchanged.

" It was an absolutely stone cold negative outcome, " said Dr. Goodman,

an associate professor of pediatrics and epidemiology at the s Hopkins

School of Medicine, who was not associated with the study. The scientists

had to declare that the screening test, seemingly so promising, should be

abandoned.

Their finding thrust them into the debate over a growing assortment of

screening tests used to search for disease in adults and children.

In an editorial with the neuroblastoma papers in The New England Journal of

Medicine last week, Dr. Cunningham of the California Department of

Health Services wrote:

" As these studies illustrate, the decision about whether or not to screen

should be driven not by the availability of a laboratory screening test, but

by careful analysis of outcomes, including saving the lives of the screened

newborns or improving the quality of their lives. "

The screening debate is far from settled.

Although he agrees with Dr. Cunningham on the need to evaluate tests, Dr.

Larry Norton, a specialist on breast cancer at the Memorial Sloan-Kettering

Cancer Center in New York and the president of the American Society for

Clinical Oncology, said he still strongly believed that early diagnosis made

biological sense.

The theory behind early diagnosis, Dr. Norton added, comes from years of

work with animals that repeatedly shows that cancers treated early can be

cured and that if they are left to grow and spread, cure becomes impossible.

" On the basis of animal models, my predisposition is to believe that early

diagnosis is a good thing, " Dr. Norton said.

He said he knew of no exceptions in the animal research. There is no reason,

he said, to think that humans are inherently different from animals. " Early

diagnosis works in animals, and basically mammals are mammals, " Dr. Norton

added.

The question, he said, is whether the screening tests are detecting cancers.

" Early diagnosis makes sense if you are diagnosing a true cancer, " he added.

In neuroblastoma, he said, the problem was that the test was not finding

true cancers. It was finding tumors that did not need to be treated and was

missing those that were deadly.

To everyone's surprise, it turned out that the supposedly rare spontaneous

regressions were actually the most common form of neuroblastoma tumors. No

one had noticed them before because, without the screening test, very few of

those tumors had ever been detected.

The Nature of Cancer

Lazy Cells Upset Traditional Ideas

Dr. Woods, a neuroblastoma expert at the Aflac Cancer Center of

Emory University in Atlanta, cited a powerful lesson: " The theory that one

can pick up all cancers early and have the outcome good is not correct, " he

said. " It certainly is not correct for neuroblastoma. "

But some are asking whether the neuroblastoma case is the exception or the

rule. That is a conundrum that hinges on an emerging and startling view of

the very nature of cancer.

Over the last few years, investigators have found more and more hints that

cancer is not what they always thought it was. The traditional view was that

cancerous cells looked aberrant under a microscope, grew in an uncontrolled

fashion and, in most cases, killed.

Now, though, researchers understand that some cancers are indolent - so

indolent, in fact, that they will never grow large enough in the patient's

lifetime to cause medical problems. Still others look like cancers under the

microscope and have growth patterns in the lab that are typical of deadly

tumors but can stop growing on their own and revert to normal tissue.

At the same time, there are more screening tests, and they are increasingly

sensitive, finding cancers at earlier stages. That leaves doctors with a

problem. The earlier they detect cells that look cancerous, the less certain

they can be of how dangerous they are.

" The whole issue of diagnosis is based on visual criteria, " said Dr. Evan R.

Farmer, a dermatologist, skin pathologist and the dean of Eastern Virginia

Medical School. " But with cancer, you are talking about what happens

biologically. If it metastasizes and kills the patient, then you know it's

cancer. If it doesn't metastasize, then you don't know if it is or isn't

cancer.

" Maybe you didn't wait long enough or maybe you treated it successfully or

maybe it had the capacity to metastasize but you removed it or maybe it

looked like cancer and you called it cancer. But in fact it didn't have the

ability to metastasize. "

Medical experts say they are agonizing over the screening questions.

" This is both an intellectual and an emotional debate, " said Dr. Isra Levy,

a cancer specialist at the Canadian Medical Association, who participated in

the study of neuroblastoma screening. " The issues are all legitimate issues,

and they are very, very difficult. We are dealing in a world where certainty

is desirable, but it isn't there. "

Even the names given to some tumors hint at their ambiguous nature. There

are " incidentalomas, " adrenal gland tumors of unknown significance that

began turning up in increasing numbers when people had C.T. scans or

M.R.I.'s for other conditions. Medical specialists do not know whether they

should be removed or left alone, but they do know that lethal adrenal

cancers are far too rare for many of those tiny tumors to be dangerous.

In cervical cancer, the most common abnormality found with Pap tests is

called " atypical squamous cells of unknown significance. "

" The name tells you how much we know about its natural history, " Dr. Barnett

Kramer, director of the Office of Disease Prevention at the National

Institutes of Health, said. The condition's significance is unclear, but to

be safe, doctors remove the abnormal cells.

Experts may not even agree about whether a cell sample looks abnormal, as

Dr. Farmer learned a few years ago. He and his colleagues asked expert

pathologists to submit what they considered classic slides of skin tumors

that were either malignant or not, examples that these specialists thought

were so clear that they could be used in a textbook. Dr. Farmer and his team

sent the slides of cells from 37 patients to eight leading pathologists.

Those experts had agreed to decide whether the tumors were cancerous or

normal or whether the category was unclear.

They looked for a disordered growth pattern in the tumor tissue. They

examined the individual cells, looking for irregular shapes and enlarged

nuclei. In just 11 of the 37 tumors did all the experts come to the same

conclusion about what they were seeing. (MY COMMENT: I don't know about you,

but this is NOT very comforting news to me. Literally, the pathologist is

deciding who has cancer and who does not and now the news is that even THEY

CANNOT AGREE. I am thinking of all the people who very well may NOT have had

cancer and yet have gone through the physical, financial and emotional

trauma of a cancer diagnosis! Actually, we have suspected that this might be

going on in the cancer industry...can we recognize the stench of greed?)

The Skewed Screenings

'Overdiagnosis': A Growing Problem

Neuroblastoma is the sole cancer in which such clear evidence exists that a

screening test did harm without doing good. But some experts say there is

reason to believe that other cancer screening tests produce similar effects,

but perhaps not as pronounced.

Those experts call the problem overdiagnosis, or finding tumors that are not

dangerous but that cannot be distinguished from ones that may become lethal.

Those experts see signs of over diagnosis in prostate cancer, where men 50

and older are urged to have a blood test known as the P.S.A. (or prostate

specific antigen); in melanoma screening, which looks for the malignant skin

cancer; and in lung cancer screening, with a new test, the spiral C.T.

Over diagnosis may also be occurring with screening for breast, cervical and

ovarian cancers.

" Over diagnosis exists in virtually every cancer, " said Dr. Otis Brawley, a

professor of medical oncology and epidemiology at the Winship Cancer

Institute of Emory University in Atlanta.

Unless it can be proved that a screening test reduces the death rate of a

cancer, researchers like Dr. Brawley, Dr. Kramer and others say, it may be

better to forgo it and wait for symptoms than to have a test. " It's the

iceberg issue, " Dr. Kramer said. " If you dip below the waterline to lesions

you've never seen before, you can't assume that because they look like

tumors we've seen before that they will have the same natural history. "

Dr. Kramer cites data from Japan on a new test to find early lung cancers.

The test, spiral C.T. scanning, is finding similar numbers of cancers in

people who never smoked as in smokers. Yet 10 times as many smokers die from

lung cancer. That, Dr. Kramer said, is a hint that the new test, like the

older ones, is finding cancers that are not dangerous.

Prostate cancer screening also raises over diagnosis questions, some

researchers say. With the widespread use of the P.S.A. test, the incidence

soared, from 143.3 cases per 100,000 in 1990, hitting a peak at 195.6 in

1992 and declining to 155.3 per 100,000 in 1998. By 1998, so many men had

already been tested that fewer new cancers were being found. But the death

rate from prostate cancer, which fell from 38.6 per 100,000 in 1990 to 32.3

per 100,000 in 1998, did not fall nearly so fast and at least part of the

decline is due to improved treatment.

" I'm very very worried, " Dr. Brawley said.

Some experts, like Dr. Ian M. Jr., a urologist at the University of

Texas Health Science Center in San , say that although some over

diagnosis of prostate cancer undoubtedly occurs the test is doing what it is

supposed to do, finding cancers early and saving lives. He is heartened by

the fact that the death rate is lower and says he sees more men with cancer

that can be treated.

Dr. has the P.S.A. test himself.

Dr. J. Feuer, a statistician at the National Cancer Institute,

cautioned that it could be difficult to interpret national cancer data

because many factors influenced the figures. In breast cancer, the incidence

has risen consistently and steadily, independent of mammography, about 1

percent a year.

In fact, Dr. Feuer said, the increase apparently began in the 1940's, long

before mammography was introduced. But it complicates attempts to interpret

trends in incidence rates.

Attempts to interpret mortality rates are complicated by the fact that

cancer treatment has been changing and improving over the years.

Dr. Norton said it would be a mistake to write off cancer screening in

general because of fears of over diagnosis. For now, he said, early

diagnosis may be the only way to cure some cancers.

Dr. Norton said that with mammography, at least, the test was finding tumors

so early that the combination of early diagnosis and improved treatment had

led to a 10 percent drop in the death rate since the early 90's.

" The package of screening and treatment is having an impact on mortality, "

he said. While over diagnosis may occur, Dr. Norton said, it may be balanced

by better outcomes for women whose cancers are found at a stage when the

treatment is more effective and less disfiguring and debilitating.

The Evaluations

Should Every Test Be Questioned?

Mammography, which is being subjected to vigorous debate, is one of the only

screening tests that has been evaluated in clinical trials.

The debate hinges on the quality of the studies that show regular screening

mammograms reduce the death rate from breast cancer. Some critics say that

the benefit is small, that it takes tens of thousands of women being

screened for years to find a savings of a few lives and that with such a

small benefit uncertainties about the study's data make them question

whether the results are solid. Other experts say the studies show that

mammograms can prevent deaths from breast cancer.

But even some who defend the mammography trials say the screening questions

have to be raised anew with each test.

" You want to apply the question to every cancer screen, " said Dr. A.

, director of the division of cancer screening at the American Cancer

Society. " You want to be sure that whatever promise it appears early

diagnosis holds, you haven't been completely blindsided. "

Dr. Freedman, a statistician at the University of California at

Berkeley, said he was also satisfied that the benefits of mammography were

demonstrated, but agreed that every screening test had to be evaluated. " You

cannot say a priori by pure reasoning that screening helps for other

diseases, " Dr. Freedman said.

Dr. Bradley Efron, a professor of statistics and health research and policy

at Stanford, faults experts who have oversimplified the case.

" The people who say, `We're saving lives,' are undoubtedly right, " Dr. Efron

said. " They probably are saving lives. But the question is, What's the cost?

We could save even more lives if all men had their prostates removed at age

50 and if all women had their breasts removed at age 50. "

If the number of lives saved is minuscule compared with the number of people

who are harmed by over diagnosis, by unnecessary treatments, by treatments

that could have been delayed with no ill effects, then the value of the test

has to be in question, he said.

" It's quite a sophisticated point, " Dr. Efron said. " I don't think you can

blame the public. I blame the medical researchers who say, 'We're saving

lives.' "

The questions are pressing because screening is different from any other

medical program, said Dr. Goodman of s Hopkins. " We bring it to healthy

people, and those who test positive become sick people, the subjects of

medical intervention, " he explained. " We need to be awfully careful. "