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Editorial |

The Importance of Negative Studies: Autofluorescence Bronchoscopy for Lung Cancer Screening FREE TO VIEW

David E. Ost, MD, MPH, FCCP
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.

University of Texas MD Anderson Cancer Center, Houston, TX

CORRESPONDENCE TO: David E. Ost, MD, MPH, FCCP, the University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1462, Houston, TX 77030


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(5):993-994. doi:10.1016/j.chest.2016.06.014
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Published online

Screening for lung cancer in appropriate high-risk groups with low-dose CT (LDCT) has been demonstrated to be effective and is now part of many practices and existing evidence-based guidelines., Effective clinical implementation of these guidelines is an ongoing process but is well under way., In this issue of CHEST, Tremblay et al provide additional useful insights into another potential method for lung cancer screening, specifically the use of autofluorescence (AF) bronchoscopy.

FOR RELATED ARTICLE SEE PAGE 1015

This was a prospective observational study nested within the Pan-Canadian Early Detection of Lung Cancer Study. The first 1,300 participants from the Pan-Canadian study with an estimated 2% or greater lung cancer risk over 5 years (as determined by a risk-prediction model derived from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial), undergoing LDCT were enrolled. Participants received AF bronchoscopy in addition to LDCT at study entry. AF bronchoscopy was performed by experienced bronchoscopists, and at least one bronchoscopist per center had prior experience with AF. Bronchoscopic quality assurance for image interpretation was conducted in a rigorous manner. LDCT detected 56 prevalent lung cancers (4.3%). AF bronchoscopy led to 776 endobronchial biopsies being performed in 333 of the 1,300 patients (25.6%). AF bronchoscopy identified one carcinoma in situ and four carcinomas. However, the only malignant lesions detected by AF bronchoscopy that were occult on CT were one carcinoma in situ and one carcinoid, so the incremental value of AF bronchoscopy when added to LDCT was 2 of 1,300 or 0.15% (95% CI, 0.0%-0.6%).

This large study merits attention because it allows physicians to assess the effectiveness of AF bronchoscopy when performed alone in a high-risk population and when performed in conjunction with the current standard of care, specifically LDCT. The extremely low incremental effectiveness of AF bronchoscopy when added to LDCT suggests that AF will not be incrementally cost-effective for lung cancer screening in this population.

In addition, the low detection rate overall (5 of 1,300 or 0.4%) suggests that AF bronchoscopy, if performed in a similar high-risk population but without LDCT, would not be effective at reducing lung-cancer-attributable mortality, since > 90% of prevalent cancers could not be identified with this technique. Notably, this was not a low-cancer-risk population. The investigators attempted and succeeded in identifying a relatively high-risk group using previously published models, since the prevalence of cancer on LDCT was 4.3% in this study. Therefore, additional refinement of the selection criteria to further enrich the population of patients with cancer to identify a suitable screening population for AF is unlikely to work.

Although this is not a surprising finding for most interventional pulmonologists, the study does provide value, just as prior negative studies using chest radiography and sputum cytologic techniques were valuable. The study shows us that it is time to close the book on AF bronchoscopy, at least in its current form, as a possible lung cancer screening strategy. The study also provides data that suggest that bronchoscopic screening of any sort will face significant challenges, since > 90% of the prevalent cancers did not arise in the central airways that are reachable by bronchoscopy.

It is also useful to consider this study in a broader context. There are an abundance of older AF bronchoscopy studies—many of which are smaller and often positive but with highly variable results.,, These were useful studies at the time, given the evidence base available. As experience grew, it became evident that clinical experience rarely matched the reported results. A well-designed multicenter prospective observational study, nested within a larger randomized controlled trial, represents a sound scientific strategy as well as a good value for the public dollar in this case, since it allows physicians to efficiently answer the question of whether or not to continue to investigate AF bronchoscopy as a lung cancer screening tool. Further small uncontrolled single-center studies at this point would not have been useful in resolving the issue. There is a time and place for case reports driven by observation, for preliminary case series data, for retrospective studies, and for prospective observational studies, depending on the nature of the question and the existing body of evidence. There are also instances when only larger and more rigorous multicenter prospective studies will be useful. This was one of those cases.

In the broader context of interventional pulmonology, this represents a successful study, since it adds to the body of knowledge in a meaningful way. It was the right study to be done at this point in time, given the evidence available up until now. The process of scientific advancement is an iterative one, characterized by hypothesis formation driven by observation followed by rigorous and efficient testing and reassessment. Negative results are common and indeed are necessary. A well-designed study can be informative, even if the results are negative. The negative results provided by these investigators are fairly definitive and will allow the interventional pulmonology community to move on in search of alternative solutions to this and other important problems. This will facilitate a shift of resources to more productive areas and will benefit patients in the long run, so even as we close the book on AF bronchoscopy, another book opens and new questions await.

Supplementary Data

Aberle D.R. .Adams A.M. .Berg C.D. .et al Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409 [PubMed]journal. [CrossRef] [PubMed]
 
Detterbeck F.C. .Mazzone P.J. .Naidich D.P. .et al Screening for lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e78S-e92S [PubMed]journal. [CrossRef] [PubMed]
 
Grosu H.B. .Eapen G.A. .Jimenez C.A. .et al Lung cancer screening: making the transition from research to clinical practice. Curr Opin Pulm Med. 2012;18:295-303 [PubMed]journal. [CrossRef] [PubMed]
 
Wiener R.S. .Gould M.K. .Arenberg D.A. .et al An official American Thoracic Society/American College of Chest Physicians policy statement: Implementation of low-dose computed tomography lung cancer screening programs in clinical practice. Am J Respir Crit Care Med. 2015;192:881-891 [PubMed]journal. [CrossRef] [PubMed]
 
Tremblay A. .Taghizadeh N. .McWilliams A.M. .et al Low prevalence of high-grade lesions detected with autofluorescence bronchoscopy in the setting of lung cancer screening in the Pan-Canadian Lung Cancer Screening Study. Chest. 2016;150:1015-1022 [PubMed]journal. [CrossRef]
 
Tammemagi M.C. .Freedman M.T. .Pinsky P.F. .et al Prediction of true positive lung cancers in individuals with abnormal suspicious chest radiographs: a prostate, lung, colorectal, and ovarian cancer screening trial study. J Thorac Oncol. 2009;4:710-721 [PubMed]journal. [CrossRef] [PubMed]
 
McWilliams A.M. .Mayo J.R. .Ahn M.I. .et al Lung cancer screening using multi-slice thin-section computed tomography and autofluorescence bronchoscopy. J Thorac Oncol. 2006;1:61-68 [PubMed]journal. [CrossRef] [PubMed]
 
Lam S. .Kennedy T. .Unger M. .et al Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy. Chest. 1998;113:696-702 [PubMed]journal. [CrossRef] [PubMed]
 
Edell E. .Lam S. .Pass H. .et al Detection and localization of intraepithelial neoplasia and invasive carcinoma using fluorescence-reflectance bronchoscopy: an international, multicenter clinical trial. J Thorac Oncol. 2009;4:49-54 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Aberle D.R. .Adams A.M. .Berg C.D. .et al Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409 [PubMed]journal. [CrossRef] [PubMed]
 
Detterbeck F.C. .Mazzone P.J. .Naidich D.P. .et al Screening for lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e78S-e92S [PubMed]journal. [CrossRef] [PubMed]
 
Grosu H.B. .Eapen G.A. .Jimenez C.A. .et al Lung cancer screening: making the transition from research to clinical practice. Curr Opin Pulm Med. 2012;18:295-303 [PubMed]journal. [CrossRef] [PubMed]
 
Wiener R.S. .Gould M.K. .Arenberg D.A. .et al An official American Thoracic Society/American College of Chest Physicians policy statement: Implementation of low-dose computed tomography lung cancer screening programs in clinical practice. Am J Respir Crit Care Med. 2015;192:881-891 [PubMed]journal. [CrossRef] [PubMed]
 
Tremblay A. .Taghizadeh N. .McWilliams A.M. .et al Low prevalence of high-grade lesions detected with autofluorescence bronchoscopy in the setting of lung cancer screening in the Pan-Canadian Lung Cancer Screening Study. Chest. 2016;150:1015-1022 [PubMed]journal. [CrossRef]
 
Tammemagi M.C. .Freedman M.T. .Pinsky P.F. .et al Prediction of true positive lung cancers in individuals with abnormal suspicious chest radiographs: a prostate, lung, colorectal, and ovarian cancer screening trial study. J Thorac Oncol. 2009;4:710-721 [PubMed]journal. [CrossRef] [PubMed]
 
McWilliams A.M. .Mayo J.R. .Ahn M.I. .et al Lung cancer screening using multi-slice thin-section computed tomography and autofluorescence bronchoscopy. J Thorac Oncol. 2006;1:61-68 [PubMed]journal. [CrossRef] [PubMed]
 
Lam S. .Kennedy T. .Unger M. .et al Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy. Chest. 1998;113:696-702 [PubMed]journal. [CrossRef] [PubMed]
 
Edell E. .Lam S. .Pass H. .et al Detection and localization of intraepithelial neoplasia and invasive carcinoma using fluorescence-reflectance bronchoscopy: an international, multicenter clinical trial. J Thorac Oncol. 2009;4:49-54 [PubMed]journal. [CrossRef] [PubMed]
 
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