In search of the holy grail: lung cancer biomarkers.

A central paradigm in the care of patients with lung cancer is to offer surgery with curative intent (and hopefully outcome) to as many patients as possible while performing as few unnecessary surgeries as possible. " Unnecessary " surgery must be defined first as surgery in patients with advanced stage disease, in whom (at this time) surgery offers no benefit over chemoradiation therapy. Exactly who meets this definition may be in flux, as trials that employ neoadjuvant chemotherapy may change the answer to the question of " who does (or does not) benefit from lung cancer surgery? " In the current setting, patients whose lung cancer is clinical stage IIIa or worse do not gain a significant benefit from surgical resection. The initial evaluation of patients with suspected lung cancer has therefore focused on determining, with the least invasive approach possible , those whose disease is N2 or worse. Biomarkers, easily detectable serum markers, are one of the highly prized targets of cancer research. Several facts about lung cancer make it unique among the common solid malignancies. Relative to other common malignancies, there is an especially high risk of morbidity from lung cancer surgery because of the population at risk for lung cancer, and the fact that it involves removal of a vital organ. Also, surgery for more advanced stage disease (most patients with IIIa and worse) offers no benefit over nonsurgical therapy. Because of these and other facts, a biomarker in lung cancer is needed not only for screening, but also as an aid in diagnosis, staging, and as a means of determining response to therapy. Features of an attractive biomarker for lung cancer would include one or more of the following: (1) in screening, either as a primary tool, or to discriminate CT screened patients with cancer from those who do not have cancer, thus eliminating the need for invasive procedures in patients with benign disease ; (2) to determine those patients with known or suspected lung cancer who are unlikely to benefit from surgery (those with bulky mediastinal lymph node enlargement due to N2 nodal involvement with cancer); (3) to signify response to therapy or lack thereof; and (4) to increase the accuracy of existing tests for diagnosis, staging, and treatment response, much like the use of the d-dimer assay in suspected venous thromboembolic disease. 1 The report by Tamura and colleagues in this issue (see page …