COMMENTARY

The Overdiagnosis Theory in Lung Cancer Screening:

Does It Make Any Sense?

RUSSELL S. KUSSMAN, MD, JD

As a medical Rip Van Winkle, I read with great (and personal)interest the October issue of JSO regarding lung cancer screening—especially the article by Strauss and Dominioni [1] about using chest X‐ray (CXR) as a screening tool and “The Time is Now” editorial byJacobson and Jaklitsch [2]. Unlike the editors, I finished my medicaltraining in the mid‐“70”s and I was never taught that “screening shouldnot be performed for lung cancer.” In my day, we often ordered CXR’sas part of “annual physicals.”Asmy own career took a twisted path awayfrom clinical and academic medicine, I was spared the “baffling” and“curious” feelings to which Drs. Jacobson and Jaklitsch refer [2].

That is, until last month. Harking back to the old days, I imploredmy primary care physician to humor me and obtain a CXR for the firsttime in years, despite no new pulmonary symptoms. Contrary to allrecommendations, guidelines and so‐called “evidence‐based”medicine,he reluctantly gave in, no doubt risking opprobrium from whateverpowers that be. I was so struck by his reluctance that I reviewed some ofthe literature on the subject and was surprised to learn that screening todetect early lung cancer has been actively discouraged since I ceased myclinical practice years ago.

It is beyond the scope of this Letter to address all the flaws, if notabsurdities, of the “over‐diagnosis” theory underpinning the rationaleagainst screening. Likewise, a discussion of how slavish devotion to“evidence‐based” medicine can distort logic and common sense, at theexpense of goodmedicine and to the detriment of patients, is a subject foranother day. But as to lung cancer, the essential questions seem clear: (1)Does early detection of lung cancer save lives? And, (2) if so, what is thebest, most cost‐effective, feasible method of early detection; and forwhat population of patients? Unfortunately, the debate and the literatureoften conflate the two questions, making their answers vague andambiguous. The claim of “overdiagnosis” is particularly insidiousbecause it undermines the first question—implying that early detectionmay do more harm than good—which obfuscates the second.

Seen from the outside by a former academic physician, turned lawyer,and now trial judge steeped in the daily assessment of facts, evidence,and proof (albeit in a far different context), the overdiagnosis theoryappears to have evolved from “Alice in Wonderland” [3] to “TheEmperor has No Clothes.” The definition itself is nebulous, even afteryears of attempted clarification and use [4]. Proof of its actual existenceremains unclear and requires “very long term follow‐up” yet to beperformed on the most recent and relevant NLST and PLCO trials [5]. Inits typical usage “overdiagnosis” refers to the finding of an actualmalignant lung tumor in a person who dies of something else, before thetumor can kill him. The implication is that since the person died ofsomething other than lung cancer, the malignancy must have been eitherindolent or clinically insignificant. Frankly, this is absurd on its face. Justbecause someone with adenocarcinoma of the lung gets run over by abus, it does not follow that his cancer was indolent or clinicallyinsignificant. No one with Stage I lung cancer would turn down apotentially curative resection because theymight get hit by a bus, or have

a heart attack or stroke, and die anyway. In short, the fact that people withlung cancer may die of something else does not and cannot define thevirulence or lethality of their tumors. We tell juries not to leave theircommon sense at home. The same goes for physicians.

Moreover, the biology of the disease must also be taken into account.If lung cancers were a slow‐growing ubiquitous tumor incidentallyoccurring in people who often die of something else, that might beanother matter. But then one would expect to frequently see suchindolent, clinically insignificant tumors at autopsy—as we do, forexample, with prostate cancer. Classical studies with that malignancyassert that the prevalence increases substantially as men age, leading to anearly 100% likelihood of finding occult prostate cancer in autopsies atage 100 [6]. But despite citation to autopsy studies by the proponents ofoverdiagnosis, they tell a far different story. For example, in a review of24,708 autopsies, 13,837 of which died of “natural causes,” there wereonly 28 cases of invasive non‐small cell lung cancers and 11 cases ofcarcinoma in situ. The rate of incidental lung cancer was only .34%, ofwhich 86% were Stage I (presumably undiagnosed before death, butcurable by resection). Although the authors of the article infer that thesefindings support the overdiagnosis theory, they candidly admit that “…[i]t is not possible to determine from the present study whether theincidental lesions were biologically indolent or would have progressedto cause death had the individuals not died from co‐morbid disease” [7].

One thing is clear: The biologic and clinical behavior of lung cancerand prostate cancer differ significantly. While “watchful waiting” maybe an option in some prostate cancers [8], no one watchfully waits aknown adenocarcinoma of the lung. Yet carried to its logical conclusion,that is precisely what overdiagnosis advocates recommend. To say thatearly detection—by whatever means—does more harm than good, onemust also believe that leaving a known lung cancer untreated because thepatient may die of something else is a reasonable option. This conclusionis not only illogical and unwarranted, it is dangerous. It undermines theincentive to do everything reasonably possible to detect lung cancerearly, while it is curable.

Also disconcerting is the reluctance to apply simple logic. Forexample, now that it has been shown by the NLST study that CTscreening lowers mortality by 20% when compared to annual chest X‐ray [9], some have questioned whether we can infer that CT screeninglowers mortality when compared to no screening at all [5]. Isn’t thatobvious? How can CT screening work better than CXR’s, but not better

*Correspondence to: Russell S. Kussman, MD, JD, Ste. #473, 1158 26th St.,SantaMonica, CA 90403. Fax: (310) 573‐0165. E‐mail: rkussman@aol.com

Received 04 October 2013; Accepted 10 October 2013

DOI 10.1002/jso.23491

Published online 19 November 2013 in Wiley Online Library(wileyonlinelibrary.com).

Journal of Surgical Oncology 2014;109:177–178

� 2013 Wiley Periodicals, Inc.

than nothing at all? Simple logic holds that if A is greater than B, and B isgreater than or equal to C, then A is greater than C. Therefore, if CTscanning is better than CXR at detecting lung cancer early, it must bebetter than no CXR at all, even if CXR is utterly worthless—the nullhypothesis notwithstanding.

With the recent randomized population trials, we are at the start of anew era in lung cancer screening with low‐dose CT scanning [10]. Yet(especially in light of the PLCO trial), some have concluded that the issueof CXR’s effectiveness as a screening tool has been put to rest [5]. This isclearly not the case, as witnessed by the compelling article by Strauss andDominioni [1]. Moreover, the argument against CXR screening againconflates the benefit of early detection with themeans of early detection.It is internally inconsistent to say it has been “…show[n] convincinglythat early detection can lower the risk of death from lung cancer” and atthe same time say that “…screening with [CXR’s] is not effective” [5].CXR screening may not be cost‐effective. It may not be reasonable as apublic health measure, given the effort, cost, and likely yield. Choosingwhich populations to screen can be problematic. But let’s stop confusingbenefit with feasibility. The fundamental point is this: If early detectionprovides a benefit, it does so regardless of how the detection occurs. It isthe feasibility of the detection method as applied to a large number ofpatients as a public health measure that limits our ability to succeed. Butif we now accept the NLSTfindings that picking up an early lesion byCTsaves lives, we cannot logically argue that picking up the exact samelesion at the exact same time by CXR, or any other technique, is of novalue. That argument simply does not hold water.

Just ask my primary care physician. He called me the evening after Iconvinced him to humor an old fogy who practiced in pre‐historic times.The adenocarcinoma found by CXR in my left lower lobe was resected afew days later. The lesion was relatively small and all lymph nodes werenegative, making me Stage IA and giving me a fighting chance atsurvival. There can be little doubt that had I acquiesced to usual care;waited until the lesion had spread or become symptomatic; or beenconcerned about overdiagnosis, I’d likely be a dead man. Anecdotal?Sure. But unlike the conflicting and confusing statistical analysesswirling around the ambiguous concept of overdiagnosis, it is logical,supported by our clinical experience, backed by common sense, andconsistent with our understanding of the pathophysiology of this disease.

In my case, no one would have thought it reasonable to ignore thetumor seen on CXR on the chance that it was indolent or clinicallyirrelevant; no onewould have altered their management because of a fearof overdiagnosis. If management is not affected by a fear ofoverdiagnosis, why should looking for it in the first place be affectedby that fear? Especially when the risk of overdiagnosis is unnecessarytreatment, but the risk of underdiagnosis is death.

It is high time to put the dangerous and illogical concept ofoverdiagnosis to rest. There is no longer any need for medical students,house officers, and attending physicians to be “baffled.”Nor is there anyneed for the survivors of those who have died since routine screeningceased in the early “80”s to be “curious” about how it took so long for usto embark upon the road we are finally traveling today.

REFERENCES

1. Strauss GM, Dominioni L: Chest X‐ray screening for lung cancer:Overdiagnosis, endpoints, and randomized population trials. J SurgOncol 2013;108:294–300.

2. Jacobson FL, Jaklitsch MT: Low‐dose CT screening for lungcancer: The time is now. J Surg Oncol 2013;108:265–269.

3. Strauss GM, Dominioni L: Perception, paradox, paradigm: Alice inthe wonderland of lung cancer prevention and early detection.Cancer 2000;89:2422–2431.

4. Bach PB: Overdiagnosis in lung cancer: Different perspectives,definitions, implications. Thorax 2008;63:298–300.

5. Sox HC: Screening for lung cancer with chest radiographs. JAMA2011;306:1916–1918.

6. Gabriel PH, Delongchamps N: Brawley O: et al: The worldwideepidemiology of prostate cancer: Perspective from autopsy studies.Can J Urol 2008;15:3866–3871.

7. Manser RL, Dodd M, Byrnes G: et al: Incidental lung cancersidentified at coronial autopsy: Implications for overdiagnosis oflung cancer by screening. Respir Med 2005;99:501–507.

8. Penney KL, Stampfer MJ, Jahn JL: Gleason grade progression isuncommon. Cancer Res 2013;73:5163–5168.

9. The National Lung Screening Trial Research Team: Reduced lung‐cancer mortality with low‐dose computed tomographic screening. NEngl J Med 2011;365:395–409.

10. Sox HC: Better evidence about screening for lung cancer. N Engl JMed 2011;365:455–457.

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