0
Editorial |

The Importance of Being Adaptable: Developing Guidelines for Lung Nodule Evaluation in Asia FREE TO VIEW

Ching-Fei Chang, MD; Michael K. Gould, MD, FCCP
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: M. G. received research funding from PCORI to perform a pragmatic trial of strategies for pulmonary nodule evaluation. None declared (C-F. C).

aDivision of Pulmonary, Critical Care, and Sleep Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA

bDepartment of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA

CORRESPONDENCE TO: Michael K. Gould, MD, FCCP, Department of Research and Evaluation, Kaiser Permanente Southern California, 100 S Los Robles, Pasadena, CA 91101


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


Chest. 2016;150(4):763-765. doi:10.1016/j.chest.2016.06.035
Text Size: A A A
Published online

More than 175 million years ago, Pangaea splintered and the continents drifted, carrying with them clusters of living organisms that would eventually develop into our myriad of current species. Like Darwin’s finches, the evolution of today’s human racial groups likely occurred as a result of both genetic inbreeding and local environmental selection pressures, such as differing climates, food resources, and endemic diseases. For this reason, it should come as no surprise that lung cancer can present and respond to therapy differently across diverse populations.

FOR RELATED ARTICLE SEE PAGE 877

Certainly, there is mounting evidence that Asians with lung cancer are a unique subgroup of patients who defy expectations regarding the standard profile of an American patient with lung cancer. In Asian countries, the average age of onset is much earlier (40s-50s), with many of the victims being lifelong nonsmokers in whom adenocarcinoma with oncogenic driver mutations develops as a result of exposure to endemic risk factors such as severe air pollution, volatile cooking oils, and pulmonary tuberculosis.,,

These unique features make it difficult to apply standardized management algorithms developed in the United States to the Asian population at large. For example, only 2% of the National Lung Cancer Screening Trial (NLST) study population were Asian, and all of them were former smokers. Risk calculators for lung nodule evaluation, such as the Mayo Clinic and VA Hospital models, were developed and validated using data from mostly whites, blacks, and Hispanics. Thus, because these types of studies form the basis of the CHEST guidelines for the evaluation and management of patients with pulmonary nodules, their recommendations may be more difficult to generalize to Asian countries.

Evidence of limited generalizability has already been established in several studies of lung cancer screening in Asia, particularly in Korea and Taiwan. For example, because many Asian patients with lung cancer are younger and do not smoke (especially women), applying NLST criteria in retrospect would have missed up to 91.6% of lung cancer cases! In these studies, in lieu of smoking, a stronger predictor appeared to be a family history of cancer (any kind) and female sex, but these are not among the official NLST screening criteria.,,,

Likewise, current American risk calculators for determining the likelihood of cancer in a nodule do not factor in the high prevalence of tuberculosis (TB) in Asia. Recent Chinese studies have linked a history of TB infection to an 11-fold increase in the development of lung cancer compared with a noninfected cohort., In addition, these calculators do not incorporate the substantial contribution of toxic air pollution, volatile cooking oil fumes, chronic exposure to incense and mosquito coil smoke, and infection with human papillomavirus,, thus raising concerns that many Asian patients may be misclassified with regard to risk stratification and then inappropriately managed.

In fact, CHEST guidelines regarding the workup and management of pulmonary nodules do not translate well in Asian settings for a number of reasons. Not only is accurate risk stratification a problem but also other barriers to implementation include (1) a limited availability of technology and expertise, especially in rural areas; (2) resource use constraints in countries with huge indigent populations; (3) cultural and religious beliefs regarding lung cancer and its treatment; and (4) a family-based approach to decision-making in lieu of patient autonomy.

In this issue of CHEST, Bai et al have endeavored to adapt the current CHEST pulmonary nodule evaluation guidelines for use in Asia. An expert panel of renowned Asian pulmonologists and thoracic surgeons was assembled in 2014 to refine and revise the CHEST guidelines using the ADAPTE method.

One of the most important points made in this revision is the impact of TB on nodule workup. Because TB is a much greater public health issue in Asia than in the United States, finding out if a nodule results from TB is just as important as finding out if a nodule results from lung cancer. Both will need to be aggressively treated. Thus in Asia, there is less reliance on the use of PET scans and more emphasis on the use of nonsurgical biopsy procedures to achieve a definitive diagnosis, especially in a moderate-risk patient.

The authors also advocate the use of telemedicine to expand on the availability of higher-level expertise. For rural areas, lung cancer evaluation can be implemented by teleradiology and phone or online multidisciplinary discussions. Telemedicine is potentially invaluable in other, perhaps unexpected, ways. In Asian culture, medical decision-making often falls into the hands of the adult children rather than the patient, so providing a means for long-distance communication between physicians and key family members would be helpful in expediting appropriate care.

Although this document is a very well-written and much needed addition to the educational resources on lung cancer in Asia, a few areas should be raised for clarification or improvement.

First and foremost, some of the revisions to the CHEST guidelines are not supported by evidence. The authors do acknowledge this, but their reasons are often unclear.

For example, the authors recommend extending the duration of CT surveillance of a solid nodule beyond 2 to 3 years. Although this is reasonable for an indolent ground-glass lesion, which may take longer than 24 months to show growth, a stable solid nodule is very unlikely to be malignant. More importantly, given the huge numbers of low-income patients who will be affected, low-value CT scanning may incur opportunity problems and actual costs (price of the scan, radiation exposure, inconvenience of travel, and time away from work) that are not negligible. If patients and primary care physicians were included in the expert panel, this particular recommendation may have been very different.

On this point, the Asian guidelines seem to conflate the related (but distinct) issues of screening vs surveillance imaging. It is reasonable to recommend long-term annual lung cancer screening with low-dose CT in appropriately selected patients at high risk for lung cancer death provided that adequate resources are available to ensure that downstream evaluation and management of screening-detected nodules is timely, safe, and effective. However, this does not imply that CT surveillance of patients with stable solid nodules should continue beyond 2 years.

Likewise, many of the recommendations require new technology and expertise to perform advanced minimally-invasive procedures such as virtual bronchoscopy, radial endobronchial ultrasonography, and navigational bronchoscopy. Even in the United States, this technology is not universally available, so the chances of it being widely accessible in Asia are even less likely. As a caveat, the guidelines state that patients with suspicious lung nodules should be referred to a center of excellence. This regionalization or centralization of care may be a viable solution in some large-city settings, but implementation may be more challenging than expected given the sheer volume of nodules encountered in practice. In addition, centralization is more costly and less convenient for patients. Differential access to lung nodule evaluation centers would likely favor more socioeconomically advantaged patients, thus creating further disparities in care.

In summary, the authors should be lauded for taking on such a challenging task. Clearly, there is a need for an Asian version of the CHEST pulmonary nodule evaluation guidelines that takes into consideration all the unique risk factors (genetic, cultural, environmental) that distinguish lung cancer in Asians from its western counterpart. However, in the absence of good data, many of the revisions are based largely on expert opinion, and only a limited number of thought leaders from pulmonary medicine and thoracic surgery were involved. Future revisions to this document may consider inclusion of a broader expert panel—regarding not only discipline (eg, medical oncology, radiation oncology, thoracic radiology, primary care, and patient advocates) but also the number of Asian countries represented, especially those of lower socioeconomic status. As with any high-quality guideline, the strength of recommendations should ideally consider the issue of affordability. The World Health Organization defines “cost-effectiveness” as anything less than three times the gross domestic product per capita per life-year saved. Thus, the inclusion of data demonstrating the solvency of these propositions in poorer countries would substantially bolster their validity.

As Bai et al have wisely acknowledged, this initial guideline is still a work in progress. We are hopeful that under the pressure of natural selection (ie, provider feedback and emerging new evidence), this important document will evolve over time into a form that will be Asia-centric, cost-effective, and embraced whole-heartedly by all involved.

References

Zhou W. .Christiani D.C. . East meets West: ethnic differences in epidemiology and clinical behaviors of lung cancer between East Asians and Caucasians. Chin J Cancer. 2011;30:287-292 [PubMed]journal. [CrossRef] [PubMed]
 
Lam W.K. . Lung cancer in Asian women—the environment and genes. Respirology. 2005;10:408-417 [PubMed]journal. [CrossRef] [PubMed]
 
Mahjub H. .Sadri G.H. . Meta-analysis of case-referent studies of specific environmental or occupational pollutants on lung cancer. Indian J Cancer. 2006;43:169-173 [PubMed]journal. [CrossRef] [PubMed]
 
Kumar V. .Becker K. .Zheng H.X. .Huang Y. .Xu Y. . The performance of NLST screening criteria in Asian lung cancer patients. BMC Cancer. 2015;15:916- [PubMed]journal. [CrossRef] [PubMed]
 
Chen C.Y. .Chen C.H. .Shen T.C. .et al Lung cancer screening with low-dose computed tomography: experiences from a tertiary hospital in Taiwan. J Formos Med Assoc. 2016;115:163-170 [PubMed]journal. [CrossRef] [PubMed]
 
Chong S. .Lee K.S. .Chung M.J. .et al Lung cancer screening with low-dose helical CT in Korea: experiences at the Samsung Medical Center. J Korean Med Sci. 2005;20:402-408 [PubMed]journal. [CrossRef] [PubMed]
 
Wu FZ, Huang YL, Wu CC, et al. Assessment of selection criteria for low-dose lung screening CT among Asian ethnic groups in Taiwan: from mass screening to specific risk-based screening for non-smoker lung cancer [published online ahead of print March 30, 2016].Clin Lung Cancer.http://dx.doi.org/10.1016/j.cllc.2016.03.004.
 
Yu Y.H. .Liao C.C. .Hsu W.H. .et al Increased lung cancer risk among patients with pulmonary tuberculosis: a population cohort study. J Thorac Oncol. 2011;6:32-37 [PubMed]journal. [CrossRef] [PubMed]
 
Wu C.Y. .Hu H.Y. .Pu C.Y. .et al Pulmonary tuberculosis increases the risk of lung cancer: a population-based cohort study. Cancer. 2011;117:618-624 [PubMed]journal. [CrossRef] [PubMed]
 
Li Y.J. .Tsai Y.C. .Chen Y.C. .Christiani D.C. . Human papilloma virus and female lung adenocarcinoma. Semin Oncol. 2009;36:542-552 [PubMed]journal. [CrossRef] [PubMed]
 
Bai C. .Choi C.-M. .Chu C.M. .et al Evaluation of pulmonary nodules: clinical practice consensus guidelines for Asia. Chest. 2016;150:877-893 [PubMed]journal
 

Figures

Tables

References

Zhou W. .Christiani D.C. . East meets West: ethnic differences in epidemiology and clinical behaviors of lung cancer between East Asians and Caucasians. Chin J Cancer. 2011;30:287-292 [PubMed]journal. [CrossRef] [PubMed]
 
Lam W.K. . Lung cancer in Asian women—the environment and genes. Respirology. 2005;10:408-417 [PubMed]journal. [CrossRef] [PubMed]
 
Mahjub H. .Sadri G.H. . Meta-analysis of case-referent studies of specific environmental or occupational pollutants on lung cancer. Indian J Cancer. 2006;43:169-173 [PubMed]journal. [CrossRef] [PubMed]
 
Kumar V. .Becker K. .Zheng H.X. .Huang Y. .Xu Y. . The performance of NLST screening criteria in Asian lung cancer patients. BMC Cancer. 2015;15:916- [PubMed]journal. [CrossRef] [PubMed]
 
Chen C.Y. .Chen C.H. .Shen T.C. .et al Lung cancer screening with low-dose computed tomography: experiences from a tertiary hospital in Taiwan. J Formos Med Assoc. 2016;115:163-170 [PubMed]journal. [CrossRef] [PubMed]
 
Chong S. .Lee K.S. .Chung M.J. .et al Lung cancer screening with low-dose helical CT in Korea: experiences at the Samsung Medical Center. J Korean Med Sci. 2005;20:402-408 [PubMed]journal. [CrossRef] [PubMed]
 
Wu FZ, Huang YL, Wu CC, et al. Assessment of selection criteria for low-dose lung screening CT among Asian ethnic groups in Taiwan: from mass screening to specific risk-based screening for non-smoker lung cancer [published online ahead of print March 30, 2016].Clin Lung Cancer.http://dx.doi.org/10.1016/j.cllc.2016.03.004.
 
Yu Y.H. .Liao C.C. .Hsu W.H. .et al Increased lung cancer risk among patients with pulmonary tuberculosis: a population cohort study. J Thorac Oncol. 2011;6:32-37 [PubMed]journal. [CrossRef] [PubMed]
 
Wu C.Y. .Hu H.Y. .Pu C.Y. .et al Pulmonary tuberculosis increases the risk of lung cancer: a population-based cohort study. Cancer. 2011;117:618-624 [PubMed]journal. [CrossRef] [PubMed]
 
Li Y.J. .Tsai Y.C. .Chen Y.C. .Christiani D.C. . Human papilloma virus and female lung adenocarcinoma. Semin Oncol. 2009;36:542-552 [PubMed]journal. [CrossRef] [PubMed]
 
Bai C. .Choi C.-M. .Chu C.M. .et al Evaluation of pulmonary nodules: clinical practice consensus guidelines for Asia. Chest. 2016;150:877-893 [PubMed]journal
 
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.

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