SEATTLE-Current screening techniques allow the early detection
of prostate cancer in large numbers of men every year. The problem
is that prostate cancer appears to be an almost ubiquitous malignancy
in men over the age of 50. The question, then, is which patients
require intervention to prevent their cancer from becoming life
threatening?
Three commonly used parameters are somewhat helpful in this regard:
Gleason grade, tumor volume, and extent of tumor infiltration,
said Michael Brawer, MD, of the University of Washington, Seattle.
In his presentation at the Pacific Northwest Cancer Foundation
Meeting on Transperineal Brachytherapy for Early Stage Prostate
Cancer, Dr. Brawer noted that a number of new markers such as
oncogenes and tumor microvasculariza-tion are currently being
evaluated.
Histologic (Gleason) grading does work, he said, in predicting
the probability of metastasis. The problem is, the majority of
cancers that are detected by early screening fall into a middle
ground where the picture is not so clear.
He said that tumor volume is also helpful in predicting metastatic
disease and seminal vesicle invasion. But it is difficult to assess
the shape and volume of a tumor by remote methods. Although transurethral
ultrasound (TRUS) is helpful in visualizing the extent of the
tumor outside of the capsule, it is not otherwise useful in staging
the cancer. "Pathologic stage and echogenicity may indicate
higher grade cancer," Dr. Brawer said, "but so far we
haven't seen any difference."
Biopsy is used to determine the extent of the tumor, ie, whether
the cancer is found on one side of the prostate (B1), both sides
(B2), or shows extracapsular extension. The more biopsy sites
that contain cancer cells, the larger the tumor volume, which
worsens the prognosis.
The best combination at present for determining prostate cancer
prognosis is biopsy, histological staging, and PSA values, he
said.
The position of the tumor may have some predictive value, but
not a great deal. "Prostate cancer likes to escape the gland
along the neurovascular bundle," Dr. Brawer said. "Cancer
in the apex has a preferred position for exiting, so this may
be a slightly worse area to find the tumor, but this hasn't been
highly predictive." He noted that DNA heterogeneity (ploidy)
also has not proved to be useful.
Newer Techniques
An area that needs further study is that of neuroendocrine differentiation
of the tumor, Dr. Brawer said. Apparently an increase in the subset
of prostate cancer cells that express neuroendocrine markers has
been correlated with an increased rate of tumor progression in
some studies, but others have shown no such correlation. Expression
of the oncogenes bcl-2 and p53 may also indicate greater tumor
progression, but again results have been mixed.
A parameter that seems especially promising, Dr. Brawer said,
is the extent of microvascularization of a particular tumor. "Tumor
angiogenesis is extremely important," he said. "Once
a neoplasm is greater than 1 mm in diameter, it has to induce
a blood supply from the surrounding tissue."
Dr. Brawer and his colleagues have quantitated microvessel density
via computer and correlated this with pathologic stage. They found
that this technique yielded a significant increase in their ability
to detect which cancers had progressed beyond the prostate, particularly
when microvessel density was more than 120 vessels/mm.
Another technique for detecting ex-traprostatic disease that has
shown good preliminary results uses reverse transcriptase PCR
(polymerase chain reaction), Dr. Brawer said. The researchers
used primers against PSA and prostate membrane antigen to probe
for small numbers of circulating cancer cells.
"There's nothing new here," he said. "We've known
cancer cells circulate. The question is, are these circulating
cells able to give rise to metastases and predict a negative outcome?"
Dr. Brawer noted that the PCR technique thus far is about 72%
to 88% as sensitive as PSA levels in predicting extraprostatic
metastases. These are encouraging results, but he noted that further
markers need to be developed to prove that those cancer cells
that can be detected actually have the potential to cause metastatic
malignancy.
