Although this post does not fall in the category of “breaking” news, the subject matter is so important in the context of today’s cancer research, diagnosis and treatment that I think it is worthwhile to address the pros and cons of screening and treatment.

Apologies to William Shakespeare for the shameless way I abused his work to pen the title of this piece, adapting the famous line from his Hamlet ‘to be or not to be’ soliloquy that says “to sleep, perchance to dream; ay, there’s the rub”.

Indeed, for today, “To screen, perchance to treat; ay, there’s the rub… “

Why a Debate?

How can this even be a debate you probably ask? What could possibly be the “con” of catching cancers early, and treating them before they cause you great harm, even death? All logic surely says if you can’t prevent cancer in the first place (for sure the BEST strategy!) then diagnose it as early as you can, and get that damn thing out of you! Right??

As it turns out, to quote this time from the Gershwins’ opera, Porgy and Bess, “it ain’t necessarily so…”

The bottom line, contrary to what most of us might intrinsically feel and believe, overdiagnosis and overtreatment of many cancers is a very serious subject and is a very considerable threat to the health and well being of far too many individuals today. In other words, and this is the final adage I will throw out at you, “just because you CAN do something, doesn’t mean you OUGHT to do it”.

I have posted recently about the report of the US expert panel that recommended against much of the “routine” PSA screening for prostate cancer that currently goes on in healthy men. You can read that post here, so I will not repeat most of that today. But I did touch on an important point – that is that fear of the “C” word may be driving our health care decisions more than logical and data and objectivity. More on that below.

The Problem of Cancer Overdiagnosis

It is not just the recent recommendations against much of the routine prostate cancer screening (via PSA) that has recently inflamed public opinion, and frankly that has confused patients, advocates and the general public. You may also recall that similarly constituted expert groups haves come out in the last 2-3 years in the same way saying that many of the routine breast cancer screening (via mammograms and other screening modalities) are leading to overdiagnosis and overtreatment of well women. The same US Preventive Services Task Force (USPSTF) as made the recent pronouncement on prostate cancer also issued controversial guidelines in the US in 2009 regarding breast cancer. A Canadian Task Force, as recently as last year issued a very similar set of recommendations and guidelines. (See also Canadian Medical Association Journal article summarizing this.)

What you may not realize is that, while breast cancer and prostate cancer screening have come under the microscope and have been the centre of public attention (in some cases greeted by applause and in other cases by outrage), the issue and the problem does not stop and start with these two more “high profile” and prevalent cancers.

For example, a US Panel has recently reviewed the benefits and harms of CT scans for lung cancer screening.

This closer examination and sober second thought will become more an more common as we ask ourselves tough questions, ones that often go against our own internal instincts.

A thought experiment to better illustrate the point.

In a wonderful blog post entitled “More diagnoses are not always a good thing” on May 31, 2012, Aaron Carroll wrote a fanciful but telling hypothetical example:

“Let’s say there’s a new cancer of the thumb killing people. From the time the first cancer cell appears, you have nine years to live, with chemo. From the time you can feel a lump, you have four years to live, with chemo. Let’s say we have no way to detect the disease until you feel a lump. The five year survival rate for this cancer is about 0, because within five years of detection, everyone dies, even on therapy.

Now I invent a new scanner that can detect thumb cancer when only one cell is there. Because it’s the United States, we invest heavily in those scanners. Early detection is everything, right? We have protests and lawsuits and now everyone is getting scanned like crazy. Not only that, but people are getting chemo earlier and earlier for the cancer. Sure, the side effects are terrible, but we want to live.

We made no improvements to the treatment. Everyone is still dying four years after they feel the lump. But since we are making the diagnosis five years earlier, our five year survival rate is now approaching 100%! Everyone is living nine years with the disease. Meanwhile, in England, they say that the scanner doesn’t extend life and won’t pay for it. Rationing! That’s why their five year survival rate is still 0%.”

He went on to say:

“You have to understand that not all cancer is fatal. Many cases might never be detected and might never cause death. But if we screen like crazy, we will pick up those cases, too. Those cancers will be treated, and that can cause both mental and physical sequelae. In other words, we may be causing harm without any actual benefit in terms of saving lives.”

How big is the problem?

In April 2010,  Drs. H. Gilbert Welch and William C. Black published a very important paper In the Journal of the (US) National Cancer Institute entitled “Overdiagnosis in Cancer”.

Before we can look at some of the data, we need to understand their definitional frame of reference. From the paper:

“What Is Cancer Overdiagnosis?

Overdiagnosis is the term used when a condition is diagnosed that would otherwise not go on to cause symptoms or death. Cancer overdiagnosis may have of one of two explanations: 1) The cancer never progresses (or, in fact, regresses) or 2) the cancer progresses slowly enough that the patient dies of other causes before the cancer becomes symptomatic. Note that this second explanation incorporates the interaction of three variables: the cancer size at detection, its growth rate, and the patient’s competing risks for mortality. Thus, even a rapidly growing cancer may still represent overdiagnosis if detected when it is very small or in a patient with limited life expectancy. Overdiagnosis should not be confused with false-positive results, that is, a positive test in an individual who is subsequently recognized not to have cancer. By contrast, an overdiagnosed patient has a tumor that fulfills the pathological criteria for cancer. “

Given this definition and framework, the authors conclude (as summarized in the abstract of this paper):

“This article summarizes the phenomenon of cancer overdiagnosis—the diagnosis of a “cancer” that would otherwise not go on to cause symptoms or death. We describe the two prerequisites for cancer overdiagnosis to occur: the existence of a silent disease reservoir and activities leading to its detection (particularly cancer screening). We estimated the magnitude of overdiagnosis from randomized trials: about 25% of mammographically detected breast cancers, 50% of chest x-ray and/or sputum-detected lung cancers, and 60% of prostate-specific antigen–detected prostate cancers. We also review data from observational studies and population-based cancer statistics suggesting overdiagnosis in computed tomography–detected lung cancer, neuroblastoma, thyroid cancer, melanoma, and kidney cancer. To address the problem, patients must be adequately informed of the nature and the magnitude of the trade-off involved with early cancer detection. Equally important, researchers need to work to develop better estimates of the magnitude of overdiagnosis and develop clinical strategies to help minimize it. “

Just last week another very powerful examination of this issue appeared in the British Medical Journal.  Authored by Ray Moynihan, Jenny Doust and David Henry, and entitled “Preventing overdiagnosis: how to stop harming the healthy” this paper once again asked tough questions about our propensity to do more harm than good despite only the best of intentions.

These authors build on the definition of “overdiagnosis” from Welch and Black:

“Narrowly defined, overdiagnosis occurs when people without symptoms are diagnosed with a disease that ultimately will not cause them to experience symptoms or early death.3 More broadly defined, overdiagnosis refers to the related problems of overmedicalisation and subsequent overtreatment, diagnosis creep, shifting thresholds, and disease mongering, all processes helping to reclassify healthy people with mild problems or at low risk as sick.8

The downsides of overdiagnosis include the negative effects of unnecessary labelling, the harms of unneeded tests and therapies, and the opportunity cost of wasted resources that could be better used to treat or prevent genuine illness. The challenge is to articulate the nature and extent of the problem more widely, identify the patterns and drivers, and develop a suite of responses from the clinical to the cultural.”

The authors go well beyond cancer in their analysis. Some of the data they present are sobering indeed (Box 1, from their article):

• Asthma—Canadian study suggests 30% of people with diagnosis may not have asthma, and 66% of those may not require medications37
• Attention deficit hyperactivity disorder—Widened definitions have led to concerns about overdiagnosis; boys born at the end of the school year have 30% higher chance of diagnosis and 40% higher chance of medication than those born at the beginning of the year46
• Breast cancer—Systematic review suggests up to a third of screening detected cancers may be overdiagnosed4
• Chronic kidney disease—Controversial definition classifies 1 in 10 as having disease; concerns about overdiagnosis of many elderly people 23
• Gestational diabetes—Expanded definition classifies almost 1 in 5 pregnant women 31
• High blood pressure—Systematic review suggests possibility of substantial overdiagnosis22
• High cholesterol—Estimates that up to 80% of people with near normal cholesterol treated for life may be overdiagnosed3
• Lung cancer—25% or more of screening detected lung cancers may be overdiagnosed56
• Osteoporosis—Expanded definitions may mean many treated low risk women experience net harm18
• Prostate cancer—Risk that a cancer detected by prostate specific antigen testing is overdiagnosed may be over 60%12
• Pulmonary embolism—Increased diagnostic sensitivity leads to detection of small emboli. Many may not require anticoagulant treatment 39
• Thyroid cancer—Much of the observed increase in incidence may be overdiagnosis28

But perhaps more than words and tables, a diagram will show the “picture” in an instant. Moynihan shows similar data adapted from Welch and Black, but below is FIGURE 7 from the Welch and Black article. It shows data from 1975 through to 2005 on the number of new cases diagnosed as compared to the number of deaths form 5 different cancers. I don’t think it is fair at all to assume that all of the increases in incidence are due to overdiagnosis per se, but the pattern is certainly very striking, isn’t it?

Whereas mortality rates are steady or declining, the new cases being uncovered are going up by leaps and bounds. And I have no doubt that if the data was available to extend this analysis to the present day, the trends would likely be even more pronounced. It does make one stop and ask, ‘How much of this is necessary vs. totally unwarranted?’

Indeed, this kind of data prompted many to ask, as did Sarah Kliff last week in a Washington Post blog: “Do we have a cancer epidemic? Or an epidemic of overdiagnosis?”

Good and penetrating question…

So, Why Can’t we Stop Ourselves?

As I myself asked in these pages about PSA screening, why it is too late (in this case after a positive PSA test) to discuss the pros and cons of investigation and/or treatment as opposed to just leaving the cancer alone?

Two simple words – “cancer” and “fear”. Despite the great strides we have made in treating and curing cancers, the very word “cancer” still conjures up in most people a fear like no other. The very thought, for most people, of knowing you have a cancer growing inside you does not allow you to ignore it on the grounds that it will do you no harm.

If a cardiologist tells you that have a mild heart murmur, you most likely will not quake in fear or demand a heart valve repair surgery. You will just learn to live with it and most likely will even ignore it totally as long as it remains asymptomatic.

But if an oncologist tells you that you have a cancer, your first thought is just as likely to be “Oh my God, I’m going to die” and the second thought that likely follows close on is apt to be “How do we get rid of it?” Ignoring it because it won’t do you harm is just not in most people’s psyche, even if it all evidence says that is what you ought to do…

I will leave the last word on this to David Ropiek, who in a very telling opinion piece on June 2, 2012 in the New York Times, entitled “Cancer on the Brain” described exactly this phenomenon – how the fear of cancer, more than any other factor, may be driving treatment decisions at the individual level, and no doubt policy decisions at the societal level.

Until we can take the abject and often mortal fear out of a cancer diagnosis, and have people realize that increasingly, cancer is NOT a disease you inevitably and invariably die from, then I think the twin genies of overdiagnosis and overtreatment will never be able to be put back into the bottle, and all the facts, data and evidence to the contrary are not going to win the day…