KWFProgBarentsz2008

From UMCN Radiology Research

Exploring the clinical value of novel high resolution anatomic and molecular / functional MR imaging in prostate cancer

Project leaders: Barentsz JO Heerschap A

Duration: 2008-2014

Research project funded by a program grant from the Dutch Cancer Foundation

Objectives

To meet the increasing clinical demand to identify and employ relevant biomarkers for non-invasive imaging of the presence, stage and aggression of prostate cancer (PCa) at high spatial resolution, we want to develop new imaging methods and translate emerging new techniques into the clinical arena. These efforts will be undertaken from the solid basis of the longstanding collaborative experience of both applicants in MR imaging of PCa cancer and of cancer models with advanced clinical and experimental MR systems (3T and 7T). In particular, we want to examine the clinical capabilities and limitations of these techniques, with the aim to improve the definition of the aggression and extent of disease and to guide the individual, patient-based management of men with primary or recurrent PCa.

Approach

With the increasing number and earlier detection of men with PCa the call for adequate imaging becomes urgent, not only for decision making in more advanced cancers but in particular for earlier stage cancers (specific diagnosis of significant tumors). We and others have demonstrated that functional and molecular MR methods are excellent potential tools for this purpose. Since the introduction of MR to address diagnostic and biomedical questions in PCa there is a continuing quest for better spatial resolution, sensitivity and specificity. Recent MR developments, such as higher field magnets in combination with approaches to assess anatomy at high resolution, vascularity, metabolism, cellular density and visualization of contrast targeted or loaded cells, promise to provide the required specifications. We have available MR systems up to 11.7 T for animal research and 7 T for clinical purposes, and new molecular MRI methods are explored with groups at the Science faculty and elsewhere. We want to employ the higher signal-to-noise and molecular specificity to improve tumor presence, aggression and extension, both locally and in lymph nodes, e.g. by increasing sensitivity for nanoparticle contrast, so that even ultra small (3 mm) lymph node metastases will be detected, or to better resolve signals of metabolites (choline) for a quantitative aggression assessment. The clinical capabilities of new techniques (and contrast agents) will be evaluated on modern clinical MR scanners (3T systems), with the help of advanced post-processing tools of our CAD group. Detection: Building on our ample experience in high resolution MRI (i.e.: dynamic contrast enhanced-, diffusion weighted-, and spectroscopic MR) we will improve the detection of PCa. E.g. reliable detection of PCa without an endorectal coil (ERC) is possible at 3T. The use of a rapid molecular MR-exam in detecting PCa will be evaluated in patients with an increased PSA level (>4 ng/l) or PSA rate. In addition, the value of a recently developed, clinically approved, 3T MR-biopsy device to detect PCa in patients with persisting increased PSA and negative TRUS biopsy will be evaluated. Localization and aggression: We attained high accuracy in localizing prostate cancer with molecular MRI at 1.5T. It will be investigated if the combination of molecular, diffusion weighted and DCE MRI at 3T, and TRUS and MR-guided biopsy will give more representative biopsy results and thus a better pre-operative prediction of tumor aggression. Also, the fusion of molecular MR data with CT, showing the dominant lesion will be used to guide IMRT with subsequent evaluation of and the clinical outcome. Local Staging: We showed improved detection of even minimal (0.5 mm) capsular penetration using 3T ERC MRI (sensitivity 87%, specificity 96%). We shall assess whether the information where minimal capsular penetration is located, alters surgical management and results (e.g. % of free resection margins, possibility for nerve sparing surgery). Nodal Staging: The primary investigator has extensive experience in using iron-nanoparticle MR-contrast to detect lymph node metastasis (MRL), showing high detection accuracy for small nodes. These findings were confirmed by a recently completed multi-center study (sensitivity and specificity both 93%). It was shown that in patients with a negative MRL lymph node dissection could be safely omitted. Even better results are obtained at 3T; currently 3 mm nodal metastases can be detected. The accuracy of this technique with high-resolution 3T MRI will be validated. In addition the role in patients with PSA relapse after therapy will be studied. By prospectively investigating the impact of local treatment of MRL detected metastatic lymph nodes, on patient outcome, the true additive value of MRL will be assessed.

Elements of innovation

Use of novel molecular and functional MRI at 3T and 7T, with the aim to improve the detection, staging, prediction of aggression of the local tumor, and the recognition of small nodal metastases in PCa.

Relevance for the mission of the Dutch Cancer Society

By using these new techniques in patients with increased PCa risk (PSA >4 ng/l) their disease can be reliably detected in an early phase. This will reduce unnecessary biopsies, and active surveillance becomes feasible. Improved recognition of minimal capsular penetration will have an important impact in the choice of the appropriate therapy, and thus will increase the chance for cure and quality of life. Reliable exclusion of small lymph node metastases will reduce the need for invasive lymph node dissection in pre- and post treated patients, and thus reduces morbidity and costs.