Diffusion-weighted magnetic resonance imaging for monitoring prostate cancer progression in patients managed by active surveillance

Objectives

We studied patients managed by active surveillance to determine whether there was a difference over time in apparent diffusion coefficients (ADCs) derived from diffusion-weighted MRI in those who progressed to radical treatment (progressors, n = 17) compared with those who did not (non-progressors, n = 33).

Methods

50 consecutive patients (Stage T1/2a, Gleason grade ≤ 3+4, prostate-specific antigen (PSA) <15 ng ml^–1, <50% cores positive) were imaged endorectally (baseline and 1–3 years follow-up) with T₂ weighted (T₂W) and echo-planar diffusion-weighted MRI sequences. Regions of interest drawn on ADC maps with reference to the T₂W images yielded ADC_all (b = 0–800), ADC_fast (b = 0–300) and ADC_slow (b = 300–800) for whole prostate (minus tumour) and tumour (low signal-intensity peripheral zone lesion in biopsy-positive octant).

Results

Tumour and whole prostate ADC_all and ADC_fast were significantly reduced over time in progressors (p = 0.03 and 0.03 for tumours, respectively; p = 0.02 and 0.007 for the whole prostate, respectively). There were no significant changes in ADC over time in non-progressors. A 10% reduction in tumour ADC_all indicated progression with a 93% sensitivity and 40% specificity (A_z of receiver operating characteristic (ROC) curve = 0.68). Percentage reductions in whole prostate ADC_all, ADC_fast and ADC_slow were also significantly greater in progressors than in non-progressors (p = 0.01, 0.03 and 0.008, respectively).

Conclusion

This pilot study shows that DW-MRI has potential for monitoring patients with early prostate cancer who opt for active surveillance.Patients with early-stage prostate cancer may be offered active surveillance because of the indolent nature of the disease in many cases. This involves regular monitoring with prostate-specific antigen (PSA) levels and repeat biopsy. Repeat biopsy is invasive, sometimes poorly tolerated and carries a risk of morbidity. Non-invasive imaging methods are therefore being explored increasingly to provide biomarkers of prostate cancer behaviour.Although T₂ weighted (T₂W) MRI is the best way of visualising anatomical detail within the prostate, it has a sensitivity of just 60–76% for disease detection within the gland, with a specificity of around 55% [1, 2]. An increasingly useful addition to conventional T₂W MRI is the use of “apparent diffusivity” (tissue water incoherent displacement over distances of 1–20 μm) to develop image contrast. Diffusion-weighted (DW) MRI has been used in both clinical and research settings to detect and evaluate a variety of tumour types [3–7]. In prostate cancer, DW-MRI is proving useful in tumour detection [8]. The apparent diffusion coefficients (ADCs) that are derived by this technique provide quantitative information on the degree to which water diffusion, including the contributions made by microcapillary perfusion and true diffusion within the extracellular space, is restricted within tissues. ADCs are therefore directly associated with coherent microvessel density and cellularity [9] and with microcapillary perfusion (which contribute to a “fast” diffusion component), and with water movement within the extracellular or intracellular space over a shorter diffusion path (which contributes to a “slow” diffusion component). We have shown previously that significant differences in tumour ADCs exist between patients with low-risk and higher-risk localised prostate cancer, and that this is the case for both the fast and the slow components [10]. Changes in ADC components in the tumour and in the surrounding normal prostate tissue have not, however, been studied previously in relation to disease progression in low-risk patients managed by active surveillance. The aim of this pilot study of patients managed by active surveillance was therefore to use DW-MRI to establish whether the changes in tumour and whole prostate ADCs in patients who progressed to radical treatment differed over time from those in patients whose disease did not progress.