0
Correspondence |

Natural History of Stage I Lung CancerResponse FREE TO VIEW

Jerome Reich, MD, FCCP; James Asaph, MD, FCCP
Author and Funding Information

Affiliations: Earl A. Chiles Research Institute, Portland, OR,  Department of Surgery, Thoracic Oncology Program, University of California San Francisco, San Francisco, CA

Correspondence to: Jerome Reich, Earl A. Chiles Research Institute, 5251 NE Glisan, Building A, Portland, OR 97213-2967; e-mail: Reichje@dnamail.com



Chest. 2007;132(6):2062-2063. doi:10.1378/chest.07-2032
Text Size: A A A
Published online

This estimate by Raz et al (July 2007)1 of surgical benefit and overdiagnosis magnitude in patients with stage I non-small cell lung cancer (LC) should be viewed with caution.

  1. The comparison of survival in operated vs unoperated persons lacks balance because the former are surgically-pathologically staged, and the latter are clinically staged. As is well known, surgery frequently upstages clinical evaluation.

  2. If the cohort declining surgery were skewed by a higher frequency of comorbidities, it would account, in part, for their diminished 5-year survival rate vs the surgically treated cohort.

  3. As the authors1 note, the systematic understaging of unoperated persons conveys an unfavorable estimate of the natural history of untreated stage I non-small cell LC (ie, reverse Will Rogers Effect).

  4. The authors1incorrectly identify pseudodisease (ie, “overdiagnosis,” “iatrogenic pseudodisease,” “lanthanic disease,” and “clinically irrelevant cancer”2) with the estimated 5-year survival rate of 11% in persons with clinical stage I disease who declined surgery. Overdiagnosed cases are represented by an undetermined proportion of the 11% of 5-year survivors who will later succumb to non-LC plus those dying of non-LC (100 − 78 = 22%) within 5 years. This figure is similar to the proportion of excess cases (attributed to overdiagnosis) in the intervention cohorts of the Mayo Clinic screening trial2(22%) and Czech screening trial3 (24%).

  5. The assignment of cause of death is problematic, particularly in persons with LC who frequently have competing, lethal comorbidities. Death certificates are inaccurate sources for this information.4 Some states assign precedent cancer as the default diagnosis when the cause is uncertain. The Mayo Clinic trial2and the Czech trial3 circumvented this difficulty by assigning a panel to review the medical records of the deceased.

  6. Because overdiagnosed persons are destined to die of other causes, their inclusion in a treated cohort generates a spurious benefit as measured by LC survival.3

  7. Survival is an invalid metric of efficacy.23 Due to the surgical mortality rate (2%) and the long-term harm of lobectomy (which foreshortens the course of older smokers’ characteristic lethal comorbidities) in understaged persons (30%) and overdiagnosed persons (22+%), a reduction in LC mortality in the remaining 40% that is sufficient to more than offset this increase in non-LC mortality must be attained to achieve a net benefit. This reduction can be achieved solely by the surgical interdiction of advanced LC, which was not achieved in the intervention cohorts of the Mayo Clinic trial2and the Czech trial.3 A preliminary assessment of the CT scan trials has, similarly, shown no reduction.3

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

The authors have no conflicts of interest to disclose.

References

Raz, DJ, Zell, JA, Ignatius, O, et al (2007) Natural history of stage I non-small cell lung cancer: implications for early detection.Chest132,193-199. [PubMed] [CrossRef]
 
Reich, JM Improved survival and higher mortality: the conundrum of lung cancer screening.Chest2002;122,329-337. [PubMed]
 
Reich, JM Assessing the efficacy of lung cancer screening [editorial].Radiology2006;238,398-401. [PubMed]
 
Kircher, T, Nelson, J, Burdo, H Inaccuracy of death certificates in assigning cause of death: the autopsy as a measure of accuracy of the death certificate.N Engl J Med1985;313,1263-1269. [PubMed]
 
To the Editor:

We agree with Drs. Reich and Asaph that our study has limitations by nature of utilizing retrospective cancer registry data. Since it would be unethical to randomize stage I non-small cell lung cancer (NSCLC) patients to treatment or no treatment, population-based observational studies are the next-best data source to describe the natural history of stage I NSCLC. As mentioned in our article,1 the lack of information on staging methods likely results in underestimation of survival in patients with untreated stage I disease. For clarification, a lung cancer-specific 5-year survival of 22% and overall survival of 11% means that for a cohort of patients with stage I NSCLC with complete follow-up, 78% will have died of lung cancer, 11% will have died of other causes, and 11% will have survived for 5 years. Assuming that 5 years is sufficient time to estimate long-term survival from lung cancer, the percentage of patients with pseudodisease can be estimated by adding the 11% of survivors to a proportion of the 11% of patients who died of other diseases who would not have died of lung cancer had they survived. While Reich and Asaph argue that overall survival is not an adequate measure of efficacy for surgical resection in stage I NSCLC, it is hard to argue with data showing the excellent overall survival of patients with surgically resected stage I NSCLC, especially small tumors, compared with the survival of patients who refuse surgical resection. These survival estimates include perioperative deaths and deaths from comorbid conditions.

References
Raz, DJ, Zell, JA, Ignatius, O, et al Natural history of stage I non-small cell lung cancer: implications for early detection.Chest2007;132,193-199. [PubMed] [CrossRef]
 

Figures

Tables

References

Raz, DJ, Zell, JA, Ignatius, O, et al (2007) Natural history of stage I non-small cell lung cancer: implications for early detection.Chest132,193-199. [PubMed] [CrossRef]
 
Reich, JM Improved survival and higher mortality: the conundrum of lung cancer screening.Chest2002;122,329-337. [PubMed]
 
Reich, JM Assessing the efficacy of lung cancer screening [editorial].Radiology2006;238,398-401. [PubMed]
 
Kircher, T, Nelson, J, Burdo, H Inaccuracy of death certificates in assigning cause of death: the autopsy as a measure of accuracy of the death certificate.N Engl J Med1985;313,1263-1269. [PubMed]
 
Raz, DJ, Zell, JA, Ignatius, O, et al Natural history of stage I non-small cell lung cancer: implications for early detection.Chest2007;132,193-199. [PubMed] [CrossRef]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543