NEW YORKAs the Early Lung Cancer Action Project (ELCAP)
continues to focus on lung cancer screening and diagnosis, a
consensus has been reached on a number of points affecting the future
of the research and variants of its single-arm design.
The International Collaboration to Screen for Lung Cancer developed a
consensus statement on the use of single-arm screening studies during
workshops at the Second International Conference on Screening for
Lung Cancer, under the leadership of Claudia Henschke, MD, PhD. Dr.
Henschke is chief of the Division of Chest Imaging and professor of
radiology, Weill Medical College, Cornell University, New York.
To increase the sample size for estimation of the yield of incidence
screens, tumor growth rates, and clinical outcomes, the consensus
statement recommends pooling of data. Furthermore, pooled analysis of
separate projects is preferred over meta-analysis of individually
reported results. The pooling is also seen as a way to create a
database sufficient to answer present and future questions about the
natural history, detection, and treatment of lung cancer.
An inter-institutional board should be created to set data and
analysis standards before pooling, the consensus statement indicates.
Suggested for pooling are data on screening protocol, detection
modality, digital CT images, pathology, staging, treatment,
follow-up, and epidemiology.
Preservation of tumor specimens for future molecular analyses is
recommended, as is collection of tissue and sputum samples to permit
testing for molecular-pathologic biomarkers.
The single-arm design for lung cancer screening trials is seen as an
evolving process responsive to changing technology. Critical to its
validity, according to the statement, are following a specified
low-dose CT screening protocol and determining the final diagnosis of
each nodule, either by follow-up CT showing no growth or a pathologic
Entry criteria and diagnostic workups may differ at each
collaborating institution but should be spelled out. All study
entrants should be invited to have annual repeat screenings.
The entire screened group should be closely followed, the
document advises. All patients after undergoing a first lung
cancer resection need to be maintained in ongoing close monitoring
for subsequent lung cancers based on the standard of care at that
individual institution. Surveillance with spiral CT is
recommended because of the 1% to 3% annual cumulative risk for a new
primary lung cancer.
The standard of care for pathologically confirmed lung cancer
universally requires treatment, the document states. If a
patient refuses definitive therapy, that patient should be followed
for ultimate outcome.
Recommendations for intervention focused on peripheral lesions, since
these constitute the majority of those identified with spiral CT. For
lesions 5 mm or smaller, high-resolution CT evaluation at 3-month
intervals without immediate surgery, as is done in ELCAP, is
Confirmation of the diagnosis in lesions 10 mm or less should be with
the least invasive procedure possible. While fine-needle biopsy is
seen as the method of choice, the document recognizes that it is not
universally available. Alternative procedures are thoracoscopy and/or thoracotomy.
Whether malignant lesions are 5 mm or less or 10 mm or less, the
current standard of care is lobectomy and lymph node sampling, the
Wedge resection should be discouraged except in special
circumstances, the statement cautions. In the case of a
patient who is managed by a wedge biopsy that is later found to be
invasive cancer, the treatment of choice is a complete lobectomy with
lymph node sampling, provided that pulmonary functions are
Other options in this situation include mediastinoscopy with watchful
waiting in the absence of a positive mediastinoscopy, or
postoperative radiation therapy. The statement notes that
surveillance in this situation may need to be more frequent than
usual, and may include serial CT scans.
For lesions larger than 1 cm, a tailored standard cancer evaluation
and management is recommended.
Recommendations for quality assurance in screening research include
the establishment of a teaching file with a lexicon of the standard
nomenclature for nodule features. In ELCAP, participating
institutions set their own inclusion criteria based on age, smoking
history, and health status. The resulting variability, the consensus
statement says, is desirable, as it provides for assessment of
Screening should be done under an approved research protocol with
informed consent. All persons who are screened should have a
physician of record who can be notified of findings by the
The document strongly recommends that screening be done at centers
committed to providing the full range of relevant interdisciplinary
support for management of each case identified.
Addressing screening techniques, conference participants agreed that
low-dose spiral CT scanning remains the standard. High-resolution
images of nodules identified in such scans are recommended for
further characterization and growth determination. In the diagnostic
workup, nodule size and volume measurements should be as
precise as possible using computer methods, the document states.
Because clinical data based on carefully characterized small
carcinomas and putative precursor lesions are sparse, the
recommendations for quality assurance of pathology advise
standardized protocols for collection and evaluation. Review of all
cases by an expert panel is urged.
In the detailed recommendations for full pathologic evaluation of
resected tissue, the document advises complete histologic examination
of the tumors, all other visible or palpable lesions, lymph nodes,
and at least 10 random sections of non-neoplastic lung and
Reports should include tumor type, size, cell type, degree of
differentiation, nuclear grade, presence or absence of stromal,
pleural, and angiolymphatic invasion, and the presence or absence of
satellite lesions and putative precursor lesions, such as atypical
adenomatous hyperplasia (AAH), squamous metaplasia and/or dysplasia,
and pneumocyte proliferations.
Subtle morphologic differences discern tobacco-related
findings, including respiratory bronchiolitis and reactive atypia
from AAH. A more complete characterization of these lesions is only
possible when non-neoplastic lung is extensively sampled, the
A statement drafted by conference participants pointed out that
smoking tobacco products is the principal cause of lung cancer.
We strongly believe that tobacco industry resources, including
the existing settlement, must support the development and application
of these new technologies to provide an opportunity for cure,
the statement said.