In this Focus issue, leaders in the field provide an update on the current status of prognostic and predictive biomarkers in oncology and debate the major challenges such as statistical validation, and appropriate use and validation of surrogate endpoints. The value of CA125 monitoring in treatment decision making for ovarian cancer, the clinical development of molecular markers to individualize adjuvant therapy in colon cancer, and guidance for physicians in critically evaluating published studies on prognostic gene-expression signatures are highlighted. This Focus provides a valuable and cutting-edge resource for clinicians and researchers.
REVIEWS
Biomarkers and surrogate end points—the challenge of statistical validation
Marc Buyse, Daniel J. Sargent, Axel Grothey, Alastair Matheson & Aimery de Gramont
doi:10.1038/nrclinonc.2010.43
Nature Reviews Clinical Oncology 7, 309-317 (2010)
The validation of predictive and prognostic biomarkers and surrogate end points requires robust statistical analysis of data gathered from multiple, large, independent studies. In this Review, Marc Buyse and coauthors discuss this validation process and the nature of biomarkers and surrogate end points. Furthermore, they consider strategies for the pragmatic evaluation of biomarkers and surrogate end points in the absence of statistical validation.
Molecular markers to individualize adjuvant therapy for colon cancer
Tara Gangadhar & Richard L. Schilsky
doi:10.1038/nrclinonc.2010.62
Nature Reviews Clinical Oncology 7, 318-325 (2010)
Prognostic and predictive markers in colon cancer might help define which patients with stage II disease are likely to benefit from adjuvant therapy. In this Review, Tara Gangadhar and Richard Schilsky discuss the recent clinical development of such markers, including microsatellite instability and 18q loss of heterozygosity. Further validation of these markers could potentially lead to the individualization of adjuvant therapy in colon cancer.
What should physicians look for in evaluating prognostic gene-expression signatures?
Jyothi Subramanian & Richard Simon
doi:10.1038/nrclinonc.2010.60
Nature Reviews Clinical Oncology 7, 327-334 (2010)
Well-developed and validated genomic signatures can lead to personalized treatment decisions resulting in improved patient management. However, the pace of acceptance of these signatures in clinical practice has been slow because many of the signatures have been developed without clear focus on the intended clinical use, and proper independent validation studies establishing their medical utility have rarely been performed. The authors of this Review focus on guidelines that physicians could refer to when evaluating studies on prognostic gene-expression signatures.
Ovarian cancer: the duplicity of CA125 measurement
Amer K. Karam & Beth Y. Karlan
doi:10.1038/nrclinonc.2010.44
Nature Reviews Clinical Oncology 7, 335-339 (2010)
Elevations in CA125 measurements often antedate any signs, symptoms or radiographic evidence of disease. Unfortunately, data favoring early therapeutic intervention for recurrent ovarian cancer are lacking. The results of a clinical trial suggest that withholding treatment in the event of isolated rising CA125 levels will not negatively impact overall survival. Women with no clinical evidence of disease should be informed about the usefulness and drawbacks of CA125 measurements, and offered the choice to pursue periodic measurements as well as other surveillance.
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