| Biologic factors |
Progressive biologic heterogeneity with transient expression of certain features is a characteristic of prostatic tumor cells. In addition, biomarkers may be affected by therapy and as-yet-uncharacterized host factors. Age and the presence of other diseases, including benign prostatic hyperplasia, also introduce variation in biomarker levels among patients. Other physiologic or pathologic processes may generate biomarker profiles similar to those found in patients with prostate cancer. Exogenous substances affect biomarker presence and concentration. Foods, drugs, and natural alternative therapies are well-known interferences. |
| Clinical pathologic factors |
There is a need to define and standardize more precisely concepts of the biologic events against which biomarkers are to be measured (eg, normal variation, prostate intraepithelial neoplasia, prostate cancer progressive states). New tools for accurate detection of prostate intraepithelial neoplasia, micrometastatic spread, and states of early and/or aggressive prostate cancer recurrence need to be developed. |
| Analytic sensitivity and detection limit |
Assay sensitivity needs to be sufficiently high to allow biomarker quantitation at concentrations that have biologic relevance (eg, high-sensitivity reverse transcriptase polymerase chain reaction assays). Clinical detection and measurement of biomarkers of this type could lead to, at worst, unnecessary investigation and therapy or, at best, unnecessary chronic anxiety for the patient. There is a lack of definition of standard procedures and quality-control schemes necessary to guarantee reproducibility of the new laboratory procedures required for detection of certain biomarkers. |
| Health service factor |
It is not sufficient for a prostate cancer biomarker to detect a particular phase of neoplasia. To be successful, the biomarker must also fit within the profile of health service factors with respect to cost-effectiveness, cost benefit, and relative value of biomarker strategy for prostate cancer burden reduction.
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| Factors That Support Advances |
| Defining the biology of prostate cancer and its processes with precision |
Enhanced interaction among investigators of different disciplines and institutions Greater appreciation of the biokinetics of both prostate cancer and its biomarkers, permitting more dynamic views of how prostate cancers evolve |
| Defining host biology: pharmacogenomics and pharmacoproteinomics |
Biologic profiling has the prospect of individualizing therapy, maximizing efficacy, and minimizing toxicity. Ideal markers would reflect both prostate cancer activity and individual sensitivity to therapy.
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| Defining biomarkers and surrogate end points |
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| Creating guidelines for appropriate clinical employment of each biomarker |
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1. Surveying the quality-control programs ongoing in the United States 2. Coordinating from a scientific point of view the activities in this area and producing guidelines for the clinical employment of cancer biomarkers 3. Standardizing the procedures 4. Developing laboratory quality-control programs for the analysis of cancer biomarkers of validated clinical relevance in multicenter clinical protocols |
| Standardization and stringency of analytic technology |
Further standardize pre-analytic, analytic, and post-analytic methodology However, standardization of biomarker assay technology involves considerations beyond analytic sensitivity and specificity. For example, advancing toward standardized technology, the advantages of comparability between various studies must be weighted against the desire and need for innovation and conditions that require protocol flexibility. |
| High-quality specimen and clinical data repository |
There is a need for specimen and data repositories that address in a bioethical manner patient consent, confidentiality, specimen provenance, technical preparation, and storage.
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