PQC - 3 Are there definable properties of pre-malignant or other non-invasive lesions that predict the likelihood of progression to metastatic disease? Background: Not all cancers detected early are worth treating. However, uncertainties about the clinical behavior of a non-malignant lesion often leads to more aggressive treatment than may be warranted, which can result in net harm to the patient. Currently, the detection of non-malignant (presumptive pre-malignant) lesions, such as so-called “in situ carcinomas” of the prostate gland or breast, are often treated vigorously because of the possibility that they are likely to adopt aggressive behaviors with time. In addition, the inherent uncertainty in predicting the outcome of a given cancer can result in poor communication of the actual risk to the patient, promoting decisions that may not be appropriate for the given benefit/risk profile. Feasibility: Major advances in genomic and proteomic technologies that can genotype and phenotype small collections of cells, together with a greater awareness of the tumor microenvironment, are resulting in a better understanding of how molecular profiles relate to phenotype. New knowledge will help determine whether malignant properties are conferred stochastically, or whether early lesions differ in their likelihood of malignant progression in definable and reproducible ways, thus allowing for more accurate prognostic determinants. Prospective studies could lead to substantial improvements in the accuracy with which the clinical behavior of a given lesion can be predicted. Implications of success: Improved prediction of clinical risk could help clinicians in communicating risk/benefit profiles for treatment options. Patients could make better-informed decisions, thus matching the diagnosis with the most appropriate treatment. These developments could also identify where therapeutic advances are most needed. Insight into the biological basis for this stratification would be an important advance, with likely relevance to analogous lesions of several tissues. These changes could improve the overall benefit of early detection by reducing the risk of harm from overtreatment. |
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