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Improved MRI Technique for Detection of Lymph Node Metastases (August
2003)
The July 19 issue of the New England Journal of Medicine reported on
"Noninvasive Detection of Clinically Occult Lymph-Node Metastases in
Prostate Cancer." The technique combines MRI imaging with intravenously
administered highly lymphotropic superparamagnetic nanoparticles
(containing iron oxide) that are taken up in lymph nodes where the
particles are internalized by macrophages. Metastatic deposits do not
concentrate the particles and are thereby identified as an uptake "void."
Currently, information as to the likelihood of nodal metastases is
principally dependent on correlation of clinical/pathological data as
presented in the Partin tables, except for instances of clinical
lymphadenopathy (usually defined as nodes > 1 cm.) that usually can be
detected by current imagining techniques and confirmed by biopsy if
indicated. However, estimates of lymph node positivity can vary widely.
For example the new Partin tables (UROLOGY, Dec., 2001) would suggest a
5-18% risk of nodal metastases in a man with PC with Stage T1c, Gleason 8,
and PSA >10 ng/ml, whereas Partin and Epstein (CANCER, Feb., 2002) would
estimate the risk at 45% if four or more core biopsies were positive and
any core had a Gleason grade of 4, regardless of the PSA value. The
recently reported radiation therapy Phase III trial (JCO, May, 2003) was
essentially based on an estimation of a 15% risk of nodal
positivity. Clearly, more accurate pretreatment information about the
nodal metastatic status would be helpful.
A Chinese group reported results of 18-F-2 Deoxyglucose Positron Emission
Tomography (PET) in men whose pelvic nodes were deemed equivocal
on CT scanning (Urologia Internationalis, Vol 70, 2003). In their study of
24 men they were able to achieve a sensitivity of 75%, and 100%
specificity based on histopathological correlation.
The NEJM report involved the study of 80 men with clinical stage T1, T2,
or T3 PC who were preoperatively imaged, first with conventional MRI, and
24 hours later with the new technique. Nodes were considered malignant if
the short axis exceeded 10 mm (or 8mm if rounded). The finding of interest
relative to this PCa Commentary article is the ability of this technique
to detect metastatic deposits in nodes that did not meet the
criteria of malignancy. Their results: 1) for nodes with a short axis of
5-10mm (n=45) - accuracy 98.9% (sensitivity 96.4%, specificity 99.3%); 2)
for nodes with short axis diameter <5 mm (n=17) - accuracy 90.4%
(sensitivity 41.1%, specificity 98.1%)
Dr. Justin Smith, Seattle Radiologist, indicates that the new MRI
technique, utilizing the contrast agent "Combidex" (Cytogen Corp), is
under review by the FDA and that it is the manufacturer's hope that the
agent will be available "soon", particularly owing to the strength of the
findings in the NEJM article. At that time, Dr. Smith expects to offer the
technique in conjunction with his ongoing interest in endorectal MRI at
First Hill Diagnostic Imaging.
Bottom Line: If both PET and ferromagnetic augmented MRI can
sustain these results with further testing, clinicians will be provided
with an improved level of sensitivity for detection of nodal metastasis
that will have an important clinical impact.
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