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 diagnosis.
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 recommended.
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 document states.
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 adequate.
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 alternative approaches.
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 radiologist.
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 cartilage-bearing airways.
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 document notes.
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.