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Improbable Estimate of Lung Cancer Mortality From Screening Trials

H. Lee Moffitt Cancer Center, Tampa, FL

To the Editor:

The recent article by Patz et al¹ titled "Estimate of Lung Cancer Mortality from Low-Dose Spiral Computed Tomography Screening Trials: Implications for Current Mass Screening Recommendations" addresses the important question whether helical computed tomography (CT) screening, detection, and intervention might be projected to reduce lung cancer mortality. In the absence of mortality data from the ongoing CT trials, the authors make several assumptions and adopt methods that lead to improbable projections of lung cancer mortality rates for two current CT screening trials (4.1 deaths per 1,000 person-years from the Mayo Clinic study²; 5.5 deaths per 1,000 person-years from Early Lung Cancer Action Project³ [ELCAP]/Cornell⁴) that exceed the mortality in the usual care arm of the Mayo trial observed 30 years ago⁵ (3.9 deaths per 1,000 person-years). These high mortality projections come from the application of the Mountain stage-specific survival rates to the cancers detected by helical screening, and then adding the "usual care" mortality (a nonstandard method).

Also, the authors do not discuss one of the most interesting features of their data. The CT trials at Mayo and Cornell seem to have detected a lung cancer–stage shift. Thirty years ago, the Mayo investigators removed the cancers detected at the first (prevalence) screen to calculate their incidence (new cancer) rate. The Mayo Lung Project–screened group found 5.5 new cancers per 1,000 person-years while the usual care group experienced 4.3 new cancers per 1,000 person-years. The current Mayo CT trial found 9.2 new cancers per 1,000 person-years, and the ELCAP trial found 9.6 new cancers per 1,000 person-years. Thus, CT screening detected almost twice the number of new cancers, but projected only a similar to slightly higher mortality rate compared with the old Mayo trial. Some might suggest that not all the CT-detected lung cancers would actually be fatal (overdiagnosis). Nevertheless, Patz et al counted all of the new cases when calculating the expected mortality.

Of greater interest is the fall in the rate of advanced cancers detected. The old Mayo study detected 3.2 stage III unresected lung cancers per 1,000 person-years (incidence rates were 0.00316 in screened, 0.00325 in usual care). In contrast, Patz et al reports that the current Mayo CT study found 1.1 new advanced stage cancers per 1,000 person-years (five stage III/IV per 4,326 person-years) while ELCAP found 0.9 new advanced stage cancers per 1,000 person-years (two stage III/IV per 2,177 person-years). While there is controversy over the merit of finding additional early-stage cases of cancer, there is little doubt about the importance of finding fewer advanced cases after multiple years of follow-up.

In summary, modeling is often presented to estimate answers in the absence of data. Nevertheless, improbable results and nonstandard methods (ie, reporting the combined usual care mortality plus CT screened group mortality as screened group mortality) and discrepancies in Table 5 of the Patz et al article (stage distributions do not add to yearly totals) suggest that this report may not be the optimal model to project the lung cancer mortality reduction of helical CT screening.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

REFERENCE

1. Patz EF Jr, Swensen SJ, Herndon JE: Estimate of lung cancer mortality from low-dose spiral computed tomography screening trials: Implications for current mass screening recommendations. J Clin Oncol 22:2202-2206, 2004[Abstract/Free Full Text]

2. Swenson SJ, Jeh JR, Hartman TE, et al: Lung cancer screening with CT: Mayo Clinic experience. Radiology 226:756-761, 2003[Abstract/Free Full Text]

3. Henschke CI, Naidich DP, Yankelevitz DF, et al: Early Lung Cancer Action Project: Initial findings on repeat screenings. Cancer 92:153-159, 2001[CrossRef][Medline]

4. Henschke CI: Early Lung Cancer Action Project: Overall design and findings from baseline screening. Cancer 89:2474-2482, 2000 (suppl 11)[CrossRef][Medline]

5. Fontana RS, Sanderson DR, Woolner LB, et al: Screening for lung cancer: A critique of the Mayo Lung Project. Cancer 67:1155-1164, 1991 (suppl 4)[CrossRef][Medline]

Related Article

• Estimate of Lung Cancer Mortality From Low-Dose Spiral Computed Tomography Screening Trials: Implications for Current Mass Screening Recommendations
  Edward F. Patz, Jr, Stephen J. Swensen, and James E. Herndon, II
  JCO 2004 22: 2202-2206 [Abstract] [Full Text]

Related Reply

• In Reply:
  Edward F. Patz, Jr, Stephen J. Swensen, and James E. Herndon
  JCO 2005 23: 2107-2108 [Full Text]

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