Tumour micro-environment in early prostate cancer managed by surveillance

Author
Dr Chris Parker cparker@icr.ac.uk
Institute of Cancer Research

The natural history of early prostate cancer is highly variable. The challenge is to distinguish between the majority of cases destined to have no clinical impact, from the minority that, if untreated, would progress to symptomatic disease. Assessment of tumour micro-environment may improve prediction of early prostate cancer behaviour.

Hypoxia is a mediator of malignant progression, with mechanisms including increased genomic instability, resistance to apoptosis, and expression of angiogenic factors. In a range human cancers, the degree of tumour hypoxia has been shown to be a significant determinant of outcome, independent of established clinical prognostic factors. Two polarographic electrode studies of human prostate cancer oxygenation have found similar levels of hypoxia to that seen in other cancer types. For example, in 55 patients with localised disease, Parker et al. observed a median pO2 of 4.9 mmHg (figure 1).

	The polarographic electrode (figure 2) is currently the gold standard method for measuring tumour oxygenation, but its use is technically demanding, and limited to accessible tumours.
There is, therefore, considerable interest in the development of alternative methods of determining tumour oxygenation, which could become a routine part of clinical practice.

A wide range of imaging techniques have been used to study the tumour micro-environment, but there is little data concerning their reproducibility and their validity as measures of oxygenation and angiogenesis. DCE MRI (figure 3)

involves the intravenous injection of a contrast agent, followed by fast MRI routines to assess blood volume, perfusion and vessel permeability within the tissue of interest. BOLD MRI (figure 4)

relies on the different magnetic properties of oxy- and deoxy-haemoglobin. Gradient echo MR sequences may be designed to be sensitive to the blood deoxy-haemoglobin concentration, which is oxygenation-dependent.

An initial study of 25 men on active surveillance for early prostate cancer is now open (figure 5)

The first milestone will be to demonstrate the reproducibility of the MRI techniques, and their validity as measures of tumour microenvironment with respect to polarographic electrode measurements and microvessel density. A subsequent study is planned to analyse the relationship between functional imaging results and clinical outcome. Imaging techniques to assess the tumour micro-environment may also enable improved radiotherapy targetting, and provide a means to test the activity of therapeutic agents designed to exploit the tumour micro-environment.