Elsevier

European Urology

Volume 55, Issue 4, April 2009, Pages 761-769
European Urology

Platinum Priority – Prostate Cancer and Bladder Cancer
Editorial by Alberto Briganti on pp. 770–772 of this issue
Combined Ultrasmall Superparamagnetic Particles of Iron Oxide–Enhanced and Diffusion-Weighted Magnetic Resonance Imaging Reliably Detect Pelvic Lymph Node Metastases in Normal-Sized Nodes of Bladder and Prostate Cancer Patients

https://doi.org/10.1016/j.eururo.2008.12.034Get rights and content

Abstract

Background

Lymph node staging of bladder or prostate cancer using conventional imaging is limited. Newer approaches such as ultrasmall superparamagnetic particles of iron oxide (USPIO) and diffusion-weighted magnetic resonance imaging (DW-MRI) have inconsistent diagnostic accuracy and are difficult to interpret.

Objective

To assess whether combined USPIO and DW-MRI (USPIO–DW-MRI) improves staging of normal-sized lymph nodes in bladder and/or prostate cancer patients.

Design, setting, and participants

Twenty-one consecutive patients with bladder and/or prostate cancer were enrolled between May and October 2008. One patient was excluded secondary to bone metastases detected on DW-MRI with subsequent abstention from surgery.

Intervention

Patients preoperatively underwent 3-T MRI before and after administration of lymphotropic USPIO using conventional MRI sequences combined with DW-MRI. Surgery consisted of extended pelvic lymphadenectomy and resection of primary tumors.

Measurements

Diagnostic accuracies of the new combined USPIO–DW-MRI approach compared with the “classic” reading method evaluating USPIO images without and with DW-MRI versus histopathology were evaluated. Duration of the two reading methods was noted for each patient.

Results and limitations

Diagnostic accuracy (90% per patient or per pelvic side) was comparable for the classic and the USPIO–DW-MRI reading method, while time of analysis with 80 min (range 45–180 min) for the classic and 13 min (range 5–90 min) for the USPIO–DW-MRI method was significantly shorter (p < 0.0001). Interobserver agreement (three blinded readers) was high with a kappa value of 0.75 and 0.84, respectively. Histopathological analysis showed metastases in 26 of 802 analyzed lymph nodes (3.2%). Of these, 24 nodes (92%) were correctly diagnosed as positive on USPIO–DW-MRI. In two patients, one micrometastasis each (1.0 × 0.2 mm; 0.7 × 0.4 mm) was missed in all imaging studies.

Conclusions

USPIO–DW-MRI is a fast and accurate method for detecting pelvic lymph node metastases, even in normal-sized nodes of bladder or prostate cancer patients.

Introduction

The presence or absence of metastatic lymph node involvement in patients with bladder or prostate cancer is of major prognostic relevance and is decisive for treatment planning. Until now, computed tomography (CT) and magnetic resonance imaging (MRI) have been the modalities of choice for the assessment of lymph nodes in bladder and/or prostate cancer patients. With these modalities, however, diagnosis is based on the size and shape of the nodes; smaller metastases often go undetected and lymph nodes with reactive hyperplasia are vulnerable to false-positive findings [1]. Indeed, recent studies have shown that meticulous lymph node dissection in patients with bladder or prostate cancer discloses a high rate of metastases (25%) in patients with preoperatively negative imaging studies [2], [3], [4], [5].

The use of lymphotropic ultrasmall superparamagnetic particles of iron oxide (USPIO) as a contrast agent for MRI enables reliable detection of metastases in normal-sized pelvic lymph nodes of patients with bladder or prostate cancer. The uptake of USPIO by macrophages in normal lymph nodes results in a signal decrease on T2/T2*-weighted magnetic resonance (MR) sequences and improves diagnostic accuracy [6], [7]. However, the reading of this technique is time consuming, since a node-by-node comparison must be made between the native MRI and a second MRI after USPIO. This requires special expertise because interpretation is rather difficult [6], [7], which explains in part why USPIO has not yet received approval by the authorities.

Diffusion-weighted MRI (DW-MRI) is a noninvasive imaging technique that yields tissue diffusion properties and therefore provides structural information on the underlying tissue. Diffusion-weighted sequences are typically T2/T2*-sensitive and potentially allow combination of cellular information with USPIO uptake in a single examination. The combination of two effects—reduced diffusion together with relatively unchanged T2/T2* after USPIO in malignant lymph nodes—leads to hyperintense signals and thus to a possibly better separation from normal lymph nodes, which are supposed to become invisible due to reduced T2/T2*.

We investigated whether pelvic lymph node metastases could be reliably detected in normal-sized nodes using a combination of USPIO-enhanced MRI and DW-MRI (USPIO–DW-MRI). If successful, this would substantially shorten the reading time for MR images and would improve the diagnostic accuracy for normal-sized metastatic lymph nodes.

Section snippets

Patients and methods

This trial was set up as a pilot study for a larger prospective clinical trial (registered with ClinicalTrials.gov, number NCT00622973) to compare the diagnostic accuracy of USPIO-enhanced MRI with that of conventional histopathology. Between May and October 2008, a series of 21 consecutive patients (4 women and 17 men; median age: 63 yr; range: 50–74 yr) with bladder cancer (n = 8), prostate cancer (n = 8), or both (n = 5) underwent MRI before and after administration of USPIO prior to surgical

Results

Intravenous injection of USPIO was well tolerated by 18 of the 21 patients. Mild adverse reactions were observed in three patients starting approximately 1 h after USPIO administration. One patient complained about mild urticaria, which disappeared after 15 min; one patient had mild diarrhea lasting a few minutes; and the third patient complained of mild nausea. None of the patients needed any medication.

Image quality, despite some distortions commonly seen on DW-MRI, was sufficient in all 20

Discussion

The present study describes a fast and reliable method for the detection of pelvic lymph node metastases using combined USPIO-MRI and DW-MRI. Three independent readers were able to exclude lymph node metastases with a high negative predictive value of 94% in a median time of 13 min per patient. Overall, diagnostic accuracies of the new reading method (first USPIO–DW-MRI) were similar to those of the classic reading method (first pre- vs post-T2-weighted USPIO), despite a much faster reading

Conclusions

The present results suggest that USPIO-enhanced MRI in combination with DW-MRI is a novel, accurate, and fast method for detecting pelvic lymph node metastases even in normal-sized nodes of patients with bladder or prostate cancer.

References (22)

  • M.G. Harisinghani et al.

    Noninvasive detection of clinically occult lymph-node metastases in prostate cancer

    N Engl J Med

    (2003)
  • Cited by (206)

    View all citing articles on Scopus
    View full text