JAMA Surg. Published online April 6, 2022. doi:10.1001/jamasurg.2022.0669
H. GilbertWelch,MD, MPH-Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston, Massachusetts.
In clinical practice to say that a person has cancer gives as little information about the possible course of his disease as to say that he has an infection. There are dangerous infections that may be fatal and there are harmless infections that are self-limited or may disappear. The same is true of cancers. Cancer is not a single entity. It is a broad spectrum of diseases related to each other only in name. George Crile,MD, cancer surgeon 1 (p128)
Dr Crile’s recognition of the heterogeneity of cancer growth
Dr Crile's recognition of the heterogeneity of cancer growth in a 1955 issue of LIFE magazine presaged why early cancer detection might defy simple intuition. It is tempting to think that cancer screening can only help individuals and that all survivors of cancer detected by screening provide powerful evidence that it saves lives. However, cancer screening is counterintuitive. It turns out that the harms are more certain than the benefits; the survivors are less likely to be evidence of its benefit and more likely to be evidence of its harms.
Dr Criles uses an analogy of a barnyard pen :
The bird is a very fast cancer (missed by screening). The bear is a slow cancer, caught by the screening but which, not screened, would have manifested itself just a little later by a clinical symptom without loss of chance. The turtle and the snail represent very slow and stagnant cancers, for which screening is useless, because they would never have manifested. The patient dies with her cancer but not because of it.
The birds have already escaped the barnyard: they are the fastest growing and most aggressive cancers, those that have already spread by the time they are detectable. Screening cannot help with the birds.
Editor's note, another representation:
Limited (or Uncertain) Benefit
The goal of cancer screening is to reduce cancer mortality. Screening tends to miss the fastest growing cancers (the birds) because these cancers have such a short time window during which they are detectable by screening, but they are not clinically evident. Furthermore, effective screening requires not only earlier detection, but also treatment initiated earlier is reliably better than treatment initiated later.
Now we can notice that as cancer treatment improves, the benefit of screening decays. If clinically detected cancer can be routinely treated successfully, the utility of cancer screening naturally falls to zero.
Poorly Recognized (or Hidden) Harms
From an individual’s perspective, overdiagnosis is the most consequential harm of screening.
Overdiagnosis is so rarely confirmed in an individual (ie, a patient with a cancer that is detected by screening but is not treated, never develops symptoms, and dies of some other cause), so there was considerable debate about whether the problem really existed.
However, overdiagnosis can be easily confirmed at the population level. Thus, debates about the existence of overdiagnosis are now largely settled and have rightly moved to the question about its frequency— and how much it matters. In the case of breast, prostate, skin, and thyroid cancer screening, patients are more likely to experience the harm of overdiagnosis than they are the benefit of screening—avoiding a cancer death.
Problem is: many individuals must be screened to potentially benefit a very few. Roughly 1000 people must be screened to avert 1 cancer death in 10years.2 Thus, questions about what happens to the other 999 individuals become relevant.
Another issue apart from overdiagnosis: false alarms affect many: there are as many as 600false-positive results in a 10-year course of mammography.3 However, the bigger problem is that many people with false-positive test results are not told that the test was wrong, but rather that something is wrong with them.
Misleading Feedback, Financial Incentives, and Distraction
These harms might be acceptable were they accompanied by substantial and certain benefit. Unfortunately, screening itself provides misleading feedback that always suggests it is more beneficial than it really is.
As shown in the example in panel B of the Figure, the proportion of late-stage cancers detected falls from 50% to 25%, despite no change in late-stage incidence. Over time, 5-year survival rises owing to the combined association of lead time and overdiagnosis bias, even if the age of death is unchanged. Survivor stories are particularly pernicious: the more overdiagnosis from screening, the more people there are who believe that they owe their life to the test—and the more popular screening becomes.4 (click on the picture below)
Editor's note: In fact, if overdiagnosis could be completely eliminated, the proportion of advanced cancers would appear to be greater in the total number of cancers minus overdiagnosis, which usually amplifies the total number of cancers. The proportion of advanced cancers is diluted in the total cancer count when the proportion of overdiagnoses is added to this total. See the screening paradox:
Pr Welsch's conclusion
Dr Crile believed that medical care should be driven by patient needs, not surgeon needs (or now, system needs). He recognized there was a price to be paid for getting ahead of symptoms. Although cancer screening may make sense in selected high-risk individuals, I believe general population screening, as currently practiced in the US, has become a huge distraction to our core work. It distracts the system away from acutely ill and injured patients: as physician performance is measured in terms of how frequently they test the well and not how well they care for the sick. General population screening distracts patients and policymakers away from the genuine determinants of human health. The tremendous resources involved in screening—in terms of money, people, and effort— would be better directed elsewhere.
1. Crile G Jr. A plea against blind fear of cancer. Life. 1955;128-142.
2. Welch HG. Evidence on cancer screening efficacy in randomized trials & effectiveness in US practice. Accessed March 2, 2022.
3. Hubbard RA, Kerlikowske K, Flowers CI, Yankaskas BC, ZhuW, Miglioretti DL. Cumulative probability of false-positive recall or biopsy recommendation after 10 years of screening mammography: a cohort study. Ann Intern Med. 2011;155(8):481-492. doi:10.7326/0003-4819-155-8- 201110180-00004
4. Raffle AE, Gray JM. Screening: Evidence and Practice. 2nd ed. Oxford University Press; 2019.