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Letters To The Editor

Response to "CT Screening for Lung Cancer: Update 2007"

Memorial Sloan-Kettering Cancer Center, New York, New York, USA

Correspondence: Peter B. Bach, M.D., Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, New York 10065, USA.

Received February 11, 2008; accepted for publication February 12, 2008.

Disclosure: This article discusses the off-label use of computed tomography devices (manufactured by General Electric and others) for screening. No potential conflicts of interest were reported by the author.

I am writing about the article called "CT screening for lung cancer: Update 2007," which appeared in the January 2008 issue of The Oncologist [1]. The article contains numerous problematic and unsubstantiated assertions, in many cases inappropriately coupled to references that are either unrelated to, or contradictory to the point made by the authors.

	UNDER "KEY CONCEPTS AND DEFINITIONS"

Top Under "Key Concepts and... Under "The Early Lung... Under "ELCAP to New... Under "Concerns About the... References

 
1. The authors tell readers that the staging system for lung cancer "is based on differences in lung cancer survival." Their reference is to the update on lung cancer staging by Mountain, which states that the lung cancer staging system is based on identifying the intersection of similar treatment options and similar outcome expectations [2].

2. The authors present the term "curability rate," although it has no concrete meaning in epidemiology. Their reference is to Martini and colleagues, where the concept of "curability rate" does not appear [3].

3. The authors present, in Figure 1, estimates of "cure rates," a concept that is not found in conventional epidemiology. They cite as their source for the cure rate estimates the "American Cancer Society Facts and Figures: 2006." Yet, no cure rates appear in that report.

4. The authors claim that there is a distinction between "baseline" and "subsequent" rounds of screening. They cite Morrison [4]. In that article, no such distinction appears. In fact, Morrison focuses on a hypothetical scenario in which only a single round of screening (i.e., only the baseline round) has been performed.

5. The authors assert that "length bias" only affects the first round of screening, again referencing Morrison [4]. Morrison's article explicitly contradicts the authors on this point, noting that length bias cannot be sequestered to certain patients in a single-arm noncomparative design (such as Early Lung Cancer Action Project [ELCAP]). The Morrison article more generally critiques the type of design pursued by ELCAP, while implicitly endorsing randomized trials such as the National Lung Screening Trial (NLST). He states that "the observed case-fatality (the ELCAP endpoint) is not an appropriate measure of the beneficial effect of screening. Outcome evaluation of a screening programme is best carried out by comparison of mortality rates in the screened population with those in another otherwise comparable unscreened population (i.e., the NLST design)."

	UNDER "THE EARLY LUNG CANCER ACTION PROJECT APPROACH"

Top Under "Key Concepts and... Under "The Early Lung... Under "ELCAP to New... Under "Concerns About the... References

 
1. The authors assert that for "curability determination, a comparison group may be formed by randomly assigning people with screen-diagnosed lung cancer to immediate or delayed treatment, as was done for prostate cancer" [5]. Yet, the study they reference did not randomize individuals after screening detection, but instead randomized patients found to have prostate cancer by a variety of means [6].

	UNDER "ELCAP TO NEW YORK ELCAP TO INTERNATIONAL ELCAP"

Top Under "Key Concepts and... Under "The Early Lung... Under "ELCAP to New... Under "Concerns About the... References

 
1. The authors state that "follow-up only extends to year 4 in the National Lung Screening Trial (NLST)." The reference they provide, to the NLST website, contradicts them: the follow-up is listed as 8 years, not 4 years.

2. They state that the "median follow-up time [in the NLST] will be 4 years in 2009." The NLST website lists enrollment dates ranging from 2002 to 2004. Thus, follow-up by 2009 will range from 5 years (i.e., 2004–2009) to 7 years (i.e., 2002–2009), and the median will lie somewhere between 5 and 7 years.

3. The authors claim that the cumulative mortality rate declined in years 5 and 6 of a study examining computed tomography screening [7]. The study referenced contains no such finding. In that study, the cumulative number of events over time (i.e., deaths from lung cancer), not the cumulative mortality rate, was examined.

	UNDER "CONCERNS ABOUT THE I-ELCAP APPROACH"

Top Under "Key Concepts and... Under "The Early Lung... Under "ELCAP to New... Under "Concerns About the... References

 
1. The authors assert that lead time and length time biases affect both the ELCAP and randomized trials of screening, providing four references. Two references are to letters the authors have written, and are thus circular. The other two are to Morrison [4] and Hanley [8]; this assertion appears nowhere in either. In fact, in Hanley [8], neither the term "lead time" nor the term "length time" is even discussed—that article focuses on a subtle point regarding the analysis of comparative screening studies where the endpoint is the mortality rate (as in the NLST) [8].

2. The authors report that, in I-ELCAP, "those who were in stage I who had no treatment all died from lung cancer," referencing their own work [9]. As noted by Yee and Lynch, the cause of death of these eight subjects was not specified in the paper that the authors reference [10].

On a potentially related point, the authors state that Figure 11 displays a comparison of individuals who did and did not receive treatment for their lung cancer. The graph leaves open some questions. For instance, if these data are meant to reflect the outcomes of the 8 untreated subjects the authors have frequently referenced in their publications, then why are there 13, not 8, events in the untreated group? Also, why is there no censoring in the untreated group (as evidenced by the fact that there are equal size steps and no tick marks in the Kaplan-Meier curve), while over the same period of follow-up, there is abundant censoring among the group of treated subjects? It would be helpful to readers if the authors would address these questions, and more generally describe the sources of data used to construct the two curves in this figure.

The evaluation of cancer screening approaches is complex, and involves many subtle epidemiologic concepts that can seem counterintuitive.

	REFERENCES

Top Under "Key Concepts and... Under "The Early Lung... Under "ELCAP to New... Under "Concerns About the... References

 

1. Henschke CI, Yankelevitz DF. CT Screening for lung cancer: Update 2007. The Oncologist 2008;13:65–78.[Abstract/Free Full Text]
2. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:1710–1717.[CrossRef][Medline]
3. Martini N, Bains MS, Burt ME et al. Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 1995;109:120–129.[Abstract/Free Full Text]
4. Morrison AS. The effects of early treatment, lead time and length bias on the mortality experienced by cases detected by screening. Int J Epidemiol 1982;11:261–267.[Abstract/Free Full Text]
5. Bill-Axelson A, Holmberg L, Ruutu M et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2005;352:1977–1984.[Abstract/Free Full Text]
6. Wilt TJ, Macdonald R, Rutks I et al. Systematic review: The comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med, 2 4, 2008 [Epub ahead of print].
7. Bach PB, Jett JR, Pastorino U et al. Computed tomography screening and lung cancer outcomes. JAMA 2007;297:953–961.[Abstract/Free Full Text]
8. Hanley JA. Analysis of mortality data from cancer screening studies: Looking in the right window. Epidemiology 2005;16:786–790.[CrossRef][Medline]
9. Henschke CI, Yankelevitz DF, Libby DM et al. International Early Lung Cancer Action Program Investigators. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006;355:1763–1771.[Abstract/Free Full Text]
10. Yee AJ, Lynch TJ. CT screening for lung cancer. N Engl J Med, 356:744–745; author reply 746–747.

This article has been cited by other articles:

				B. A. Chabner Preserving the Sacred Bond: An Audit Must Be Performed Oncologist, September 1, 2008; 13(9): 922 - 922. [Full Text] [PDF]

				P. B. Bach Untreated Patients in "CT Screening for Lung Cancer: Update 2007" Oncologist, September 1, 2008; 13(9): 1030 - 1032. [Full Text] [PDF]

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