2005 Publication

Abstract: Advances in genomics, proteomics and molecular pathology have generated many candidate biomarkers with potential clinical value. Their use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. However, translation from bench to bedside outside of the research setting has proved more difficult than might have been expected. Understanding how and when biomarkers can be integrated into clinical care is crucial if we want to translate the promise into reality.

Summary:

• The TNM staging system (based on a combination of tumour size or depth (T), lymph node spread (N), and presence or absence of metastases (M)) provides a basis for prediction of survival, choice of initial treatment, stratification of patients in clinical trials, accurate communication among healthcare providers, and uniform reporting of the end result of cancer management.
• There is a dilemma in TNM staging: frequent revisions to include new biomarkers would undermine the value conferred by the stability and universality of TNM, but a static formulation of TNM risks falling behind the state of the art in diagnostic techniques, biological concepts and biomarkers.
• Biomarkers initially considered for cancer screening or risk assessment might also prove useful for cancer staging or grading.
• A biomarker for use in staging or grading need not be as specific as it must be for screening, early detection or risk assessment.
• As molecularly targeted cancer therapeutics become more common, assessing the intended target will more often be deemed necessary for prediction of clinical response, independent of TNM stage. Targeted therapies and their associated biomarkers will often 'co-evolve'.
• The ideal biomarker assay for staging should be sensitive, specific, cost-effective, fast, and robust against inter-operator and inter-institutional variability. It must also demonstrate clinical value beyond that of the other types of information that are already available at the time of diagnosis.
• Biomarker candidates must undergo clinical validation before receiving US Food and Drug Administration approval. For most candidate markers, that process is just beginning.
• Despite all of the potentially useful biomarkers — for example, those identified from microarray or mass spectrometry studies — almost none have been incorporated into formal TNM staging.