Clinical aspects of metastases

In the short term the major hope for reducing cancer mortality is to effect a reduction in the number of patients who develop malignant disease and in the proportion of cancer patients who present with metastases. Hitherto the major emphasis of clinical research on metastases has been directed at detection and elimination rather than prevention or early diagnosis. Extensive data relating histological class and tumour stage to risk of metastasis and metastatic pattern have been compiled from studies of relapse and from invasive and non-invasive staging procedures. However, the biological events involved in the metastatic process and the factors which influence it in relation to the natural history of primary human tumours are poorly understood. Information describing metastatic heterogeneity in individual patients, in terms of therapeutic response or intrinsic sensitivity to cytotoxic agents, is scanty. Similarly, the characteristics of human metastases in relation to the clonal heterogeneity of primary tumours are poorly defined. The clinical application of molecular biological techniques, which has led to the association of gene amplification with tumour behaviour in a range of sites, offers the prospects of improved tumour localization and therapy and, in the longer term, of tumour control by interventions based on a knowledge of the mechanisms that regulate cell growth and differentiation.