Changing paradigm and priorities

Ming-Sound Tsao, MD, FRCPC, is a Clinical Scientist in the Depart­ ment of Pathology, University Health Net work, and Department of Laboratory Medicine and Pathobiology, University of Toronto. Email: [email protected] INTRoDuCTIoN Lung cancer is the leading cause of cancer-related death worldwide among males, and the second leading cause among females. In 2008, it accounted for 13% (1.6 million) of all cancer deaths worldwide. Despite recent data showing decreasing incidence in developing countries and notable advancements in its early detection and treatment, lung cancer is still projected to be the sixth leading cause of death in 2030, advancing from the ninth position in 2002. In North America and Canada, the mortality rate of lung cancer is greater than the next 3 most common cancers combined: colorectal, breast and prostate cancer. Currently as many as half of new lung cancer patients are former smokers who had quit for more than 10 years. This is due to significant lag time between carcinogenic initiation and development of invasive cancers, such that the benefits of smoking cessation take approximately 20 years to realize. Importantly, lung cancers of never-smokers demonstrate distinct clinical features and associations when compared to those of smokers, accounting for at least 20% of lung cancer cases worldwide and being more common among females. Thus, lung cancer will remain a major health burden worldwide for many years to come. Currently, the overall 5-year survival rate for all lung cancer patients is approximately 15%. This poor overall rate reflects largely the fact that around two-thirds of patients are initially diagnosed with advanced stage disease with very little possibility of cure by surgery. The treatment of lung cancer patients is based primarily on the histologic diagnosis of the tumour and the stage of the disease. Two major histologic types with different biology and therapeutic responses are recognized: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).4 SCLC is a highly aggressive cancer with almost all patients presenting with advanced locoregional or systemic metastases at diagnosis. Therefore, SCLC patients are rarely treated by surgery but mainly by chemotherapy, to which it is highly sensitive. Yet, despite the high initial response rate, very few SCLC patients are curable and their median survival time is approximately 18 months. In contrast, NSCLC is a very heterogeneous disease with approximately 80–85% being represented by adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Importantly, about one-third of NSCLC patients present with tumours that are still localized to the lung or immediate local lymph nodes, and thus can potentially be cured by complete surgical resection. AbstrAct T he last decade has witnessed the dramatic coming of age of targeted therapy in lung cancer. Several new targeted drugs have been approved but only for use in a subgroup of patients whose tumours harbour the genetic/molecular aberrations targeted by these drugs. In addition, several drugs are used only in lung cancer patients with specific histologic subtypes, as the latter may define efficacy or risk of toxicity. These recent developments have required pathologists to provide a more precise diagnosis of the tumour type, as well as additional molecular data on the presence or absence of the targetable molecular aberrations. Thus, pathology practice is not just diagnostic for cancer, but has to provide information on predictive biomarkers to guide drug selection. As more and more drugs and treatment options will be based on the molecular charac teristics of the tumour, pathology practice must also embrace and adopt the new advances being achieved in molecular medicine and targeted therapy. The ability to meet the challenges presented by the changing paradigm in cancer treatment will define the future role of pathologists and pathology departments.