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Early detection

The case for early detection

Nature Reviews Cancer volume 3, pages 243–252 (2003)Cite this article

Key Points

  • The promise of early detection is that it will identify cancer while still localized and curable, preventing not only mortality, but also reducing morbidity and costs.

  • Cervical cancer is a historical illustration of the promise of early detection; countries with broad screening programmes have markedly reduced disease-related deaths. However, the efficacy and practicality of screening tests for most other cancers remain controversial.

  • The advent of new technologies — including transcript (gene-expression) analysis, genomic DNA-based methods and proteomics — offer many new opportunities for developing biomarker-based tests that are less expensive and more accurate than existing screening tests.

  • To develop and fully evaluate a new screening test requires attention to all phases of biomarker development, including identification of promising biomarkers, production of assays that can detect both clinical and pre-clinical disease, development of tests that combine sensitive biomarkers to achieve greater diagnostic accuracy, and evaluation of the impact of the tests on disease mortality and costs.

  • With many potential biomarkers in the early-detection pipeline, it will be important to develop strategies for evaluating the benefits and costs of biomarker-based tests within a reasonable time frame.

  • The dissemination of screening tests that have been inadequately evaluated can have grave consequences, including invasive follow-up of healthy individuals, morbidity from unnecessary treatment and vastly increased costs to the medical system. Although randomized screening trials remain the ultimate test of screening efficacy in preventing disease-specific mortality, it will be important to develop these and other analytical approaches so that inferences about screening costs and benefits can be made in an efficient and timely fashion.

Abstract

Early detection represents one of the most promising approaches to reducing the growing cancer burden. It already has a key role in the management of cervical and breast cancer, and is likely to become more important in the control of colorectal, prostate and lung cancer. Early-detection research has recently been revitalized by the advent of novel molecular technologies that can identify cellular changes at the level of the genome or proteome, but how can we harness these new technologies to develop effective and practical screening tests?

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Figure 1: Relative survival (5 year or 10 year) among cancer cases diagnosed with distant, regional or distant, and localized disease by year of diagnosis.
Figure 2: Phases of biomarker development.
Figure 3: Length bias and overdiagnosis in cancer screening studies.
Figure 4: Population studies of prostate cancer screening.

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Acknowledgements

Supported in part by cooperative agreement from the National Cancer Institute. We thank R. Smith of the American Cancer Society and the anonymous referees for helpful comments on an earlier version of this article.

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Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, 98109, Washington, USA

    Ruth Etzioni, Nicole Urban, Scott Ramsey, Martin McIntosh, Stephen Schwartz, Brian Reid, Jerald Radich, Garnet Anderson & Leland Hartwell

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DATABASES

Cancer.gov

breast cancer

cervical cancer

colorectal cancer

lung cancer

oesophageal cancer

ovarian cancer

prostate cancer

LocusLink

ERBB2

PSA

Glossary

PROTEOMICS

The characterization and quantification of proteins and protein systems. Proteomics methods allow for the comparison of patterns of proteins isolated from bodily fluids or cells, in normal versus diseased subjects.

FALSE-NEGATIVE RATE

The proportion of diseased subjects that test negative.

FALSE-POSITIVE RATE

The proportion of non-diseased (healthy) subjects that test positive.

OVERDIAGNOSIS

The detection by screening of disease that, in the absence of screening, would not have been diagnosed within the lifetime of the patient.

SIGMOIDOSCOPY

A test that is used to detect colo-rectal cancer. A thin, flexible, hollow tube (sigmoidoscope) is inserted into the rectum for imaging of the lower part of the colon and rectum.

COLONOSCOPY

Similar to sigmoidoscopy, but examines the entire length of the colon.

SENSITIVITY

The proportion of diseased subjects that test positive.

SPECIFICITY

The proportion of non-diseased (healthy) subjects that test negative.

PROSTATE-SPECIFIC ANTIGEN

(PSA). A glycoprotein that is produced primarily by the epithelial cells of the prostate gland. PSA levels in serum are generally low but increase in most patients with prostate cancer.

GENE-EXPRESSION ANALYSIS

The measurement of the expression of thousands of genes simultanously.

PAPANICOLAU (PAP) SMEAR

An exfoliative cytological staining procedure that can detect premalignant and malignant changes in the cervical epithelium and that is named after its founder.

HUMAN PAPILLOMAVIRUS

(HPV). A virus that causes genital warts. It has also been shown to cause cervical cancer.

T-TEST

A statistical procedure for comparing measurements in two groups or samples. The result of a t-test provides an assessment of the difference between the average value in each sample relative to the variability in the two samples.

RECEIVER-OPERATING CHARACTERISTIC (ROC) CURVE

A graph of the false-negative rate versus the false-positive rate corresponding to a biomarker-based test, as the threshold biomarker level (or cutoff) for declaring the test positive varies.

CLUSTER ANALYSIS

A technique for grouping a collection of objects into subsets or clusters such that those within each cluster are more closely related to one another than are objects assigned to different clusters.

SUPPORT VECTOR MACHINES

A technique for separating data points into classes. Support vector machines derive nonlinear boundaries to optimally separate clouds of points.

ELISA

(Enzyme-linked immunosorbent assay). A widely used technique for determining the presence or amount of protein in a biological sample, using an enzyme that bonds to an antibody or antigen and causes a colour change.

SELDI-TOF

(Surface-enhanced laser desorption — time of flight). A method for profiling a population of proteins in a sample according to the size and net electrical charge of the individual proteins. The position of an individual protein in the spectrum produced corresponds to its 'time of flight' because the small proteins fly faster and the large proteins fly more slowly.

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Etzioni, R., Urban, N., Ramsey, S. et al. The case for early detection. Nat Rev Cancer 3, 243–252 (2003). https://doi.org/10.1038/nrc1041

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