Elsevier

European Urology

Volume 56, Issue 6, December 2009, Pages 981-988
European Urology

Prostate Cancer
A Study of Diffusion-Weighted Magnetic Resonance Imaging in Men with Untreated Localised Prostate Cancer on Active Surveillance

https://doi.org/10.1016/j.eururo.2008.11.051Get rights and content

Abstract

Background

Markers that predict the behaviour of localised prostate cancer are needed to identify patients that require treatment.

Objective

We have analysed the apparent diffusion coefficient (ADC) generated from diffusion-weighted magnetic resonance imaging (DW-MRI) with respect to repeat biopsy findings and time to radical treatment in patients in a prospective study of active surveillance.

Design, setting, and participants

Some 86 men recruited between 2002 and 2006 were followed for a median of 29 mo. Patients had clinical stage T1/T2a N0/Nx M0/Mx adenocarcinoma of the prostate, prostate-specific antigen (PSA) level <15 ng/ml, Gleason score ≤7, primary Gleason grade ≤3, and positive biopsy cores (pbc) ≤50%.

Measurements

All patients had DW-MRI in addition to standard MRI sequences. Tumour regions of interest (ROIs) were identified using T2-weighted fast-spin echo images as focal areas of restricted diffusion. Univariate analyses including all clinical variables and tumour ADC data were performed with respect to repeat biopsy findings and time to radical treatment. Receiver operating curves (ROC) compared predictive variables.

Results and limitations

Patients in the study had a median age of 66 yr and a median initial PSA level of 6.7 ng/ml. Some 39 patients (45%) received deferred radical treatment, and 34 patients (40%) had adverse histology on repeat biopsy. According to univariate analysis, tumour ADC was a significant predictor of both adverse repeat biopsy findings (p < 0.0001; hazard ratio [HR]: 1.3; 95% confidence interval [CI]: 1.1–1.6), and time to radical treatment (p < 0.0001; HR: 1.5; 95% CI: 1.2–1.8). ROC curves for ADC showed an area under the curve (AUC) of 0.7 for prediction of adverse repeat biopsy findings and an AUC of 0.83 for prediction of radical treatment.

Conclusions

In patients with low-risk, localised disease, tumour ADC on DW-MRI may be a useful marker of prostate cancer progression and may help to identify patients who stand to benefit from radical treatment. This possibility warrants further study.

Introduction

Prostate cancer is the most prevalent malignancy in men in the United Kingdom, with approximately 30 000 new cases per year. On the one hand, radical prostatectomy has been shown, in a high-quality, randomised controlled trial, to provide an overall survival advantage compared with watchful waiting [1]. On the other hand, prostate cancer can often behave in an indolent fashion even without treatment, with no effect either on health or on longevity [2]. In such cases, radical treatment, with its risks of incontinence and impotence, would present a greater burden to the patient than the disease. A conventional approach is to stratify patients into risk groups according to their serum prostate-specific antigen (PSA) levels, biopsy Gleason scores, and clinical tumour stages [3], [4], [5]. These risk groups have been shown to predict the probability of biochemical recurrence after radical treatment and used as a guide to treatment decision making. However, these risk groups account for only a moderate degree of the variability in prostate cancer behaviour. Patients with low-risk and some with intermediate-risk, localised disease are often faced with the difficult decision of whether or not to have treatment by weighing the potential survival benefit against the known morbidity. There is a major, unmet need for noninvasive markers of prostate cancer behaviour within the low- and intermediate-risk groups that will identify which patients need to be treated, and conversely, which patients can safely avoid treatment. At present, imaging has no established role in risk stratification [6].

Diffusion-weighted magnetic resonance imaging (DW-MRI) provides information derived from the molecular movement of water in biological tissues. The degree of motion measured by DW-MRI relates to the mean path length travelled by water molecules. Longer path lengths are associated with higher apparent diffusion coefficients (ADCs). The three-dimensional diffusion of water within a tissue is not truly random because cell membranes impede diffusion. In the case of a highly cellular tissue, the effect of an increased number of cell membranes may significantly impede the motion of extracellular water leading to a lower path length and, hence, produce a lower ADC value. Consequently, parameters derived from DW-MRI may indirectly provide information regarding the cellularity of a given tissue [7], [8]. The normal anatomical structure of the prostate consists of a glandular component with intervening stromal tissue. This normal glandular component allows relatively unhindered motion of tissue water. As cancer becomes more poorly differentiated, however, the cellularity increases and the glandular architecture becomes unrecognisable [9], [10]. DW-MRI has been shown to discriminate cancer tissue from benign peripheral tissue and central gland tissue [11]. We have previously shown that the ADC of tumours classified as high or intermediate risk is lower than that of low-risk prostate cancer [12]. We hypothesised that, within the group of men with low- or intermediate-risk disease, tumour ADC would be a marker of disease progression. Cases with more highly cellular tumours (lower ADC values) may behave in a more aggressive fashion than cases with less cellular tumours (higher ADC values). To address this hypothesis, we studied men with untreated localised prostate cancer on active surveillance, and we analysed the results of DW-MRI with respect to repeat biopsy results and time to radical treatment.

Section snippets

Methods

A prospective study of active surveillance of localised prostate cancer was initiated at the Royal Marsden Hospital in 2002. Eligible patients had clinical stage T1/T2a N0/Nx M0/Mx adenocarcinoma of the prostate with serum PSA level < 15 ng/ml, Gleason score ≤7, primary Gleason grade ≤3, and positive biopsy cores (pbc) ≤50%. Monitoring included serial PSA measurement (monthly in the first year, every 3 mo thereafter) and repeat prostate biopsies. Repeat biopsies were performed between 12 mo and

Results

Patients were followed for a mean of 29 mo. Repeat biopsy data were available in 80 patients (93%); 34 patients had adverse repeat biopsy findings. Of the six patients for whom repeat biopsy data were not available, three patients had radical treatment based on biochemical progression; one patient had a radical prostatectomy for worsening lower urinary tract symptoms; and two patients declined to have repeat biopsies. Overall, 39 patients (45%) had deferred radical treatment. Of the 39 patients

Discussion

Using DW-MRI data on patients in a prospective study of active surveillance for localised prostate cancer, we have demonstrated that a low ADC is associated with adverse histology on repeat biopsy and shorter time to deferred radical treatment. Our analysis supports the hypothesis that, in addition to the already available biochemical and histologic data, tumour ADC may be a useful marker of the biological behaviour of prostate cancer in patients managed with an expectant policy with low- and

Conclusions

Tumour ADC on DW-MRI may be a useful marker of prostate cancer behaviour, with potential to improve patient selection for active surveillance and to offer a noninvasive technique for monitoring the disease. These possibilities warrant further study.

References (27)

  • M.J. Zelefsky et al.

    Predictors of improved outcome for patients with localized prostate cancer treated with neoadjuvant androgen ablation therapy and three-dimensional conformal radiotherapy

    J Clin Oncol

    (1998)
  • A.R. Cabrera et al.

    Prostate cancer: is inapparent tumor at endorectal MR and MR spectroscopic imaging a favorable prognostic finding in patients who select active surveillance? Radiology

    (2008)
  • M. Castillo et al.

    Apparent diffusion coefficients in the evaluation of high-grade cerebral gliomas

    Am J Neuroradiol

    (2001)
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