Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Apr 21;100(8):1219-29.
doi: 10.1038/sj.bjc.6604999.

Prognostic markers in cancer: the evolution of evidence from single studies to meta-analysis, and beyond

R D Riley  1 , W Sauerbrei, D G Altman
Affiliations
Review

Prognostic markers in cancer: the evolution of evidence from single studies to meta-analysis, and beyond

R D Riley et al. Br J Cancer. .

Abstract

In oncology, prognostic markers are clinical measures used to help elicit an individual patient's risk of a future outcome, such as recurrence of disease after primary treatment. They thus facilitate individual treatment choice and aid in patient counselling. Evidence-based results regarding prognostic markers are therefore very important to both clinicians and their patients. However, there is increasing awareness that prognostic marker studies have been neglected in the drive to improve medical research. Large protocol-driven, prospective studies are the ideal, with appropriate statistical analysis and clear, unbiased reporting of the methods used and the results obtained. Unfortunately, published prognostic studies rarely meet such standards, and systematic reviews and meta-analyses are often only able to draw attention to the paucity of good-quality evidence. We discuss how better-quality prognostic marker evidence can evolve over time from initial exploratory studies, to large protocol-driven primary studies, and then to meta-analysis or even beyond, to large prospectively planned pooled analyses and to the initiation of tumour banks. We highlight articles that facilitate each stage of this process, and that promote current guidelines aimed at improving the design, analysis, and reporting of prognostic marker research. We also outline why collaborative, multi-centre, and multi-disciplinary teams should be an essential part of future studies.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Types of prognostic marker studies, modified from Altman and Lyman (1998).
Figure 2
Figure 2
Requirements of a prognostic marker for acceptance in clinical practice, modified from Simon and Altman (1994).
Figure 3
Figure 3
Factors to consider in the design of a high-quality phase III study, modified from Altman and Lyman (1998).
Figure 4
Figure 4
Summary of important issues for the analysis of single prognostic marker studies (Holländer and Sauerbrei, 2006).
Figure 5
Figure 5
Guidelines for reporting the results of a prognostic marker study (Riley et al, 2003).
Figure 6
Figure 6
Summary of the potential benefits of having individual patient data (IPD) for a meta-analysis of prognostic marker studies.
Figure 7
Figure 7
Pathways to high-quality evidence regarding the prognostic ability of a marker, following publication of initial hypothesis generating studies.
See this image and copyright information in PMC

References

    1. Altman DG (2001) Systematic reviews of evaluations of prognostic variables. BMJ 323: 224–228 - PMC - PubMed
    1. Altman DG, De Stavola BL, Love SB, Stepniewska KA (1995) Review of survival analyses published in cancer journals. Br J Cancer 72: 511–518 - PMC - PubMed
    1. Altman DG, Lausen B, Sauerbrei W, Schumacher M (1994) Dangers of using ‘optimal’ cutpoints in the evaluation of prognostic factors. J Natl Cancer Inst 86: 829–835 - PubMed
    1. Altman DG, Lyman GH (1998) Methodological challenges in the evaluation of prognostic factors in breast cancer. Breast Cancer Res Treat 52: 289–303 - PubMed
    1. Altman DG, Royston P (2000) What do we mean by validating a prognostic model? Stat Med 19: 453–473 - PubMed

Publication types