MRI, spectroscopy combo promising for prostate cancer treatment
Although prostate cancer (PCa) screening has led to increased detection of small-volume low-grade organ-confined cancer, better methods of discriminating between clinically insignificant and significant disease are needed to further improve patient management. According to a study published this month in the journal Radiology, the combination of MRI and MR spectroscopic imaging findings and molecular marker analysis of biopsy samples could help differentiate between clinically insignificant and significant cancers and favorably affect treatment selection.

Researchers from the Memorial Sloan-Kettering Cancer Center and the Herbert Irving Comprehensive Cancer Center in New York City retrospectively assessed whether MRI and MR spectroscopic imaging and selected molecular markers correlated with each other and with clinically insignificant and significant PCa, as defined at surgical pathologic analysis.

Imaging and pathologic data for 67-year-old patient with PSA level, 9.4 ng/mL (9.4 µg/mL); PCa stage, T2a; and biopsy Gleason score, 6; resulting in combined MR imaging and MR spectroscopic imaging score of 1 (probable insignificant cancer). (a) MR spectroscopic imaging (volume excitation with water and lipid suppression by means of spectral-spatial pulses; 1000/130; chemical shift imaging matrix, 16x8x8; field of view, 110x55x55 mm; spatial resolution, 6.9 mm; one signal acquired; and imaging time, 17 minutes) grid superimposed on transverse T2-weighted MR image (4000/102; echo train length, 12; field of view, 14 cm; acquisition matrix, 256x192; section thickness, 3 mm; no intersection gap; and four signals acquired). (b) Corresponding spectroscopic grid shows voxel (*) suspicious for cancer. Images and caption courtesy of RSNA.
“Three specific markers were selected on the basis of their reported association with PCa progression: Ki-67, a proliferation marker; phospho-Akt (pAkt), a serinethreonine kinase critical to signal transduction pathways involved in cell proliferation, apoptosis and angiogenesis; and androgen receptor (AR), the phosphoprotein that mediates the actions of male sex hormones by acting as a transcription factor and interacting with the phosphoinositide 3-kinase pathway,” the scientists wrote.

Out of a total cohort of 363 patients who underwent combined endorectal MR imaging and MR spectroscopic imaging from Nov. 1999 through March 2004, 89 men gave informed consent for tissue collection and molecular marker studies. The MR studies were performed with a 1.5-T system (Excite, GE Healthcare) and endorectal coil (Medrad).  Image acquisition was followed by MR spectroscopic imaging with point-resolved spatial selection voxel excitation and band selective inversion with gradient dephasing or spectral-spatial pulses for water and lipid suppression, the authors reported.

The MRI studies were interpreted by a radiologist and the MR spectroscopic imaging data were analyzed by a physicist with more than five years experience in prostate MR spectroscopic imaging. The physicist estimated tumor volumes by multiplying the voxel size by the number of suspicious voxels.

“The MR spectroscopic readings were provided to the same radiologist who read the MR images, who then assigned an overall combined MR imaging and MR spectroscopic imaging score for the suspicion of clinically insignificant PCa in the whole gland, as seen at combined MR imaging and MR spectroscopic imaging,” the authors wrote.

Surgical pathologic analysis identified 21 (24 percent) patients with clinically insignificant PCa and 68 (76 percent) patients with clinically significant PCa.

“Regardless of whether the tumors assessed at immunohistochemicalstaining were the same ones seen at imaging, our data demonstrated that as the MR imaging score for the whole gland increased, so did molecular marker expression in the representative tumor lesion assessed,” the researchers noted. “Our study was not about assessing tumor localization by using MR imaging or combined MR imaging and MR spectroscopic imaging; rather, it concerned the capacity of MR to help make an overall assessment of clinically insignificant or significant cancer.

The scientists reported that in differentiating between clinically insignificant and significant PCas, the areas under the receiver operating characteristic curves for Ki-67, AR, pAkt, MR imaging, and combined MR imaging and MR spectroscopic imaging were 0.75, 0.78, 0.80, 0.85, and 0.91, respectively.

“We believe that we are at the beginning of a new era where imaging and pathologic examination can provide more than just tumor detection and grading,” the authors wrote. “In future prospective studies with larger patient populations, the selected markers should be evaluated in the biopsy tissue, as they may provide pretreatment quantitative data on the biologic properties of the tumor.”