Tumor perfusion assessed by dynamic contrast-enhanced MRI correlates to the grading of renal cell carcinoma: Initial results

Abstract

In this study, we investigated whether assessment of the tumor perfusion by dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) enables to estimate the morphologic grading of renal cell carcinomas.

A total of 21 patients with suspected renal cell cancer were examined using a Gadobutrol-enhanced, dynamic saturation-recovery, turbo-fast, low-angle shot sequence. Tumor perfusion and the tissue–blood ratio within the entire tumor and the most highly vascularized part of the tumor were calculated according to the model of Miles. Immediately after examination, patients underwent surgery, and the results from imaging were compared with the morphological analysis of the histologic grading.

Fourteen patients had G2 tumors, and seven patients had G3 tumors. Significantly higher perfusion values (p < 0.05) were obtained in G3 tumors than in G2 tumors when the entire tumor area was considered (1.59 ± 0.44 (ml/g/min) vs. 1.08 ± 0.38 (ml/g/min)) or its most highly vascularized part (2.14 ± 0.89 (ml/g/min) vs. 1.40 ± 0.49 (ml/g/min)). By contrast, the tissue–blood ratios did not differ significantly between the two groups.

In conclusion, unlike tissue–blood ratio, surrogate parameters of the tumor perfusion determined by DCE MRI seem to allow an estimation of the grading of renal cell carcinoma. However, further studies with high case numbers and including patients with G1 tumors are required to evaluate the full potential and clinical impact.

Introduction

Renal cell carcinoma accounts for 3% of all adult malignancies and is the most lethal of the urological cancers [1]. The usual treatment for renal cell carcinoma is nephrectomy with complete removal of the affected organ, as established by Robson et al. [2]. However, during the past decade, open nephron-sparing surgery has become established as a safe and effective alternative to radical nephrectomy in elective situations. The advantage of organ-preserving surgery is the reduced risk of subsequent renal failure with the consecutive need for dialysis. According to the latest guidelines of the European Association of Urology, the standard indications for nephron-sparing surgery can be elective (healthy contralateral kidney), relative (affected contralateral kidney that might impair future renal function) and absolute (anatomical or solitary kidney). Patients with a tumor diameter of less than 4 cm who undergo nephron-sparing surgery have similar recurrence-free and long-term survival rates as those who undergo radical nephrectomy. Where resection is performed for an absolute indication, the risk of developing a local recurrent tumor seems to be elevated, probably because of the size (more than 4 cm) and grading of the tumor [3]. While the first question can be elucidated by high-resolution imaging [4], up to now the latter has not been assessable by noninvasive imaging.

In a previous study, a relationship was reported between the grading and extent of microvessel density in renal cell carcinoma [5]. Thus, assessing tumor vascularization using imaging techniques might permit noninvasive determination of the tumor grade, in order to determine the appropriate surgery (e.g., organ-sparing vs. total nephrectomy) in patients with renal cell carcinoma. Furthermore, knowledge of the grading of renal cell carcinoma may be useful for planning and monitoring anticancer therapy regimens. If radiotherapy is chosen, tumor areas with a high nuclear grade may be irradiated at a higher dose. The efficacy of new molecular-targeted drugs such as receptor tyrosine kinase inhibitors may also correlate with the nuclear grade and angiogenic activity of tumors, and it may be necessary to adapt or rearrange the individual dose of the drug [6], [7].

Quantitative assessment of the tumor vascularization demands appropriate imaging techniques. In preclinical research, dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is an established technique for assessing the physiologic state of tumor vascularization in vivo [8]. Due to the fact that clinical MR systems and contrast agents can be used, DCE MRI is being translated into the clinical routine to an increasing degree [9]. In principle, fast T1-weighted sequences are used to acquire repetitive images during i.v. contrast administration. This enables to assess the kinetics of tumor enhancement, which are displayed as time–intensity curves [9], [10]. The shape of these curves can be characterized by descriptive terms such as the initial slope, time-to-peak, peak enhancement or area-under-the-curve. These terms are often used, but only indirect descriptors for the real tissue perfusion or blood volume. Moreover, these parameters are highly influenced by the individual cardiac output, the body-mass index or the age of a patient. In contrast to these estimates, quantitative determination of physiologic parameters is possible by using pharmacokinetic modelling (e.g., first-pass analyses [11] or two-compartment models [12], [13]).

As a consequence, we evaluated in a clinical study whether quantitative parameters of vascularization, as assessed by DCE MRI, are capable of indicating the grade of renal cell carcinoma.