Introduction: Non-Small Cell Lung Cancer

Article Outline

• Copyright

Lung cancer is an impressive disease. As we are all acutely aware, it claims more lives than any other cancer and its incidence continues to rise. Clinicians and scientists alike have struggled to classify lung neoplasms based on histopathology and behavior. These differences have led to the separation of small cell cancer from non-small cell lung cancers (NSCLCs), which make up the vast majority of cases. However, NSCLC is by no means one entity; intriguingly, the closer we look at NSCLC, and the more we dissect it, the more complex and beguiling it becomes. Clearly there is much work to be done and over the past few years tremendous advances have been made. This issue of Seminars in Oncology is dedicated to reviewing these advances and providing a glimpse of what we can expect to see in the future.

As the saying goes: an ounce of prevention is worth a pound of cure. The same could be said for early cancer detection, and so Ashton and Jett review the principals of screening and the current status of these programs. Lung cancer screening has been given a boost by the introduction of novel imaging techniques such as low-dose spiral computed tomography, positron emission tomography scans, and florescence bronchoscopy. Expanding knowledge of cancer biology has led to the identification of high-risk genetic and proteomic biomarkers as reviewed by Wardell and Massion. The combination of these biologic features with cancer imaging technologies will be a particularly powerful tool for screening and early detection.

Staging of the mediastinum is a pivotal step in the accurate assessment of patients who are potential candidates for curative thoracic surgery. Pass reviews this critical issue with particular attention to the role of minimally and non-invasive staging procedures.

Despite improvements in staging and surgical techniques, postoperative recurrence rates have been high. Although successful in other solid tumours, until recently there was little evidence to support the routine use of adjuvant chemotherapy for NSCLC. Landmark trials reported in 2003–04 have clearly demonstrated the success of this approach and, as outlined by Domont and colleagues, adjuvant chemotherapy now represents the standard of care for many patients with resected NSCLC.

A common clinical problem, the management of locally advanced NSCLC is rife with controversy. Reviewed in detail by West and Albain, the optimal strategy revolves around rigorous staging and necessitates a multidisciplinary approach including consideration of chemotherapy, radiation, and surgical resection. As the survival of patients with locally advanced disease continues to improve, there is a rising concern over the rate of relapse in the brain, often a “sanctuary” site for malignancy. Prophylactic cranial radiation has been successfully used in patients with small cell lung cancer and is an active area of research in NSCLC as discussed by Choo and colleagues.

Unfortunately, the majority of people with NSCLC present with advanced disease that requires a palliative treatment approach. Multiple studies have demonstrated that cytotoxic chemotherapy is not only cost-effective but can prolong survival and improve a patient’s quality of life. Milton and Miller review the current standard of care and discuss the recent advances in chemotherapy delivery and novel drug regimens. Although conventional chemotherapy is a valuable treatment modality, advances in cancer biology have led to the development of more tumour-specific targeted therapies. These agents show great promise when used alone or in combination and though there is still much to be learned, this is undoubtedly the future of oncology. An update on the present state of targeted therapy for NSCLC and a look forward is provided by Isobe and colleagues.

Not only have targeted therapies brought about novel treatment strategies but they have also served to highlight some of the biologic diversity that exists in NSCLC. Although bronchioloalveolar carcinoma has been distinguishable for decades, it has recently come to the forefront of NSCLC research and may be instrumental in our increasing understanding of targeted therapies. The natural history, pathology, and treatment of BAC are reviewed by Laskin and colleagues.

Vogelzang and collaborators have reviewed another unique subtype of NSCLC, malignant mesothelioma. The incidence of this relatively uncommon asbestos-related tumor is on the rise and the trend is expected to continue. Novel chemotherapy agents and molecularly targeted therapies now offer considerable hope for patients with this difficult cancer.

This is an exciting time to be working on lung cancer. The rapidly accumulating knowledge of cancer biology combined with the improvements in conventional cytotoxic chemotherapy, radiation therapy, surgical techniques, and cancer imaging have just begun to make a significant impact on the outcome of people with NSCLC. We have endeavored to create a collection of articles that not only review the current standards of care but also provide insight into the future of cancer medicine.