Assessment of Prostate Cancer Aggressiveness Using Dynamic Contrast-enhanced Magnetic Resonance Imaging at 3 T

doi:10.1016/j.eururo.2013.05.045

European Urology

Volume 64, Issue 3, September 2013, Pages 448-455

https://doi.org/10.1016/j.eururo.2013.05.045 Get rights and content

Abstract

Background

A challenge in the diagnosis of prostate cancer (PCa) is the accurate assessment of aggressiveness.

Objective

To validate the performance of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of the prostate at 3 tesla (T) for the assessment of PCa aggressiveness, with prostatectomy specimens as the reference standard.

Design, settings, and participants

A total of 45 patients with PCa scheduled for prostatectomy were included. This study was approved by the institutional review board; the need for informed consent was waived.

Outcome measurements and statistical analysis

Subjects underwent a clinical MRI protocol including DCE-MRI. Blinded to DCE-images, PCa was indicated on T2-weighted images based on histopathology results from prostatectomy specimens with the use of anatomical landmarks for the precise localization of the tumor. PCa was classified as low-, intermediate-, or high-grade, according to Gleason score. DCE-images were used as an overlay on T2-weighted images; mean and quartile values from semi-quantitative and pharmacokinetic model parameters were extracted per tumor region. Statistical analysis included Spearman's ρ, the Kruskal-Wallis test, and a receiver operating characteristics (ROC) analysis.

Results and limitations

Significant differences were seen for the mean and 75th percentile (p75) values of wash-in (p = 0.024 and p = 0.017, respectively), mean wash-out (p = 0.044), and p75 of transfer constant (K^trans) (p = 0.035), all between low-grade and high-grade PCa in the peripheral zone. ROC analysis revealed the best discriminating performance between low-grade versus intermediate-grade plus high-grade PCa in the peripheral zone for p75 of wash-in, K^trans, and rate constant (K_ep) (area under the curve: 0.72). Due to a limited number of tumors in the transition zone, a definitive conclusion for this region of the prostate could not be drawn.

Conclusions

Quantitative parameters (K^trans and K_ep) and semi-quantitative parameters (wash-in and wash-out) derived from DCE-MRI at 3 T have the potential to assess the aggressiveness of PCa in the peripheral zone. P75 of wash-in, K^trans, and K_ep offer the best possibility to discriminate low-grade from intermediate-grade plus high-grade PCa.

Introduction

Prostate cancer (PCa) is the most common malignancy in the Western male population and the third leading cause of cancer-related death in developed countries [1]. Primary methods to diagnose PCa are prostate-specific antigen (PSA) and digital rectal examination (DRE), usually followed by transrectal ultrasound (TRUS) systematic biopsy. Histopathology of the biopsy ultimately confirms the presence and the Gleason score (GS) of PCa. Characterization of PCa based on the combination of PSA level, DRE findings, and the GS from TRUS biopsy are used for the choice of treatment. However, both PSA and DRE have a low specificity and a low sensitivity [2]. In addition, TRUS biopsies are invasive, have a relatively low sensitivity, and tend to underestimate the GS and thus aggressiveness [3], [4]. Because not all PCas are life-threatening, accurate assessment of aggressiveness is essential to prevent overdiagnosis and thus overtreatment of indolent cancers [5].

Magnetic resonance imaging (MRI) will play an important upcoming role in the diagnosis and management of PCa. In addition to T2-weighted (T2w) imaging for detailed anatomical information, functional MRI techniques for additional information such as diffusion-weighted imaging (DWI), MR spectroscopic imaging (MRSI), and dynamic contrast-enhanced (DCE) MRI have already proved their usefulness in the detection of PCa [6].

DCE-MRI is based on the permeability of blood vessels and extravasation of contrast agent into the surrounding tissue. In PCa, fast angiogenesis results in the formation of leaky endothelia with a higher permeability than normal vessels. When a contrast agent is administered into the vessels it will leak out of the capillaries into tissue, where it temporarily changes the T1 relaxation time. A straightforward way of representing contrast-related signal intensity changes is with semi-quantitative parameters. These parameters are derived from a signal intensity-time curve and are relatively easy to calculate, but they may not accurately reflect the contrast concentration in tissue. Quantification of contrast leakage by pharmacokinetic modeling represents direct vascular information by estimating the concentration of contrast leakage into tissue. This is challenging, though, because multiple approaches for calibration and modeling exist, and each model makes its own assumptions that may not be valid for every tissue or tumor type.

In a recent discussion about the value of MRI in PCa, authors proposed the need for implementing multiparametric MRI assessment with defined thresholds that should contribute to the prevention of overdetection and overtreatment of indolent PCa [7]. A few studies have already shown that DWI and MRSI have the potential to assess the aggressiveness of PCa [8], [9], [10]. For DCE-MRI at 1.5 Tesla (T), results are inconsistent regarding correlations with aggressiveness and GS [11], [12], [13], [14], [15]. Literature about the use of DCE-MRI for assessing PCa aggressiveness at 3 T is lacking. Before a full multiparametric MRI protocol can be implemented for the characterization of PCa, each technique has to be evaluated for its value prior to combining all the techniques together.

Our purpose was to validate retrospectively the performance of semi-quantitative parameters and pharmacokinetic model parameters derived from DCE-MRI of the prostate at 3 T for assessing PCa aggressiveness, with the GS of cancer foci from prostatectomy specimens as the reference standard.

Section snippets

Patient characteristics

The institutional review board waived the need for informed consent. Between 2007 and 2009, all patients with newly biopsy-proven organ-confined PCa who had undergone a 3 T MR examination with the use of an endorectal coil including DCE-MRI prior to radical prostatectomy (RP), without any previous therapy for PCa, were enrolled in the study.

Data acquisition

All imaging was performed using a 3 T whole-body system (Magnetom Trio, Siemens, Erlangen, Germany). An endorectal coil (MEDRAD Inc, Pittsburgh, PA, USA)

Results

A total of 15 patients were excluded from the analysis because the entire PZ consisted of PCa and thus did not contain non-cancer PZ tissue as a reference for calibration (n = 2); cancer covered both PZ and TZ, so a clear distinction of origin could not be made (n = 2); no reliable pathology results (n = 1) were available; patients only had lesions of insignificant size (<0.5 cm³; n = 9); or the endorectal coil was not filled with perfluorocarbon (n = 1).

Overall, 57 clinically significant cancer

Discussion

This study showed that both quantitative (K^trans and K_ep) and semi-quantitative (wash-in and wash-out) parameters derived from DCE-MRI can be helpful tools to assess PCa aggressiveness in the PZ. For the parameters that either positively or negatively correlated with aggressiveness, differences in median ranks between low-grade and high-grade PCa were found, but not with intermediate-grade PCa. Although there is a significant difference between low-grade and high-grade PCa in the PZ,

Conclusions

Quantitative parameters (K^trans and K_ep) and semi-quantitative parameters (wash-in and wash-out) derived from DCE-MRI have the potential to assess PCa aggressiveness in the PZ at 3 T, despite overlap between aggressiveness classes. P75 of wash-in, K^trans, and K_ep offer the best possibility to discriminate low-grade from intermediate-grade plus high-grade PCa. These initial results are preliminary but promising for selecting those patients with organ-confined low-aggressive PCa suitable for

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Prostate CancerAssessment of Prostate Cancer Aggressiveness Using Dynamic Contrast-enhanced Magnetic Resonance Imaging at 3 T

Abstract

Background

Objective

Design, settings, and participants

Outcome measurements and statistical analysis

Results and limitations

Conclusions

Introduction

Section snippets

Patient characteristics

Data acquisition

Results

Discussion

Conclusions

J Urol

Urol Oncol

Eur Urol

Eur Urol

Clin Radiol

Eur J Radiol

Urology

Global cancer statistics

CA Cancer J Clin

Concordance between Gleason scores of needle biopsies and radical prostatectomy specimens: a population-based study

BJU Int

Screening and prostate-cancer mortality in a randomized European study

N Engl J Med

Prostate cancer: multiparametric MR imaging for detection, localization, and staging

Radiology

Relationship between apparent diffusion coefficients at 3.0-T MR imaging and Gleason grade in peripheral zone prostate cancer

Radiology

Diffusion-weighted endorectal MR imaging at 3 T for prostate cancer: tumor detection and assessment of aggressiveness

Radiology

Diffusion-weighted and dynamic contrast-enhanced MRI of prostate cancer: correlation of quantitative MR parameters with Gleason score and tumor angiogenesis

AJR Am J Roentgenol

Prostate tissue composition and MR measurements: investigating the relationships between ADC, T2, K(trans), v(e), and corresponding histologic features

Radiology

Prostate Cancer
Assessment of Prostate Cancer Aggressiveness Using Dynamic Contrast-enhanced Magnetic Resonance Imaging at 3 T