Prostate Cancer
Markers
The markers defined below include:
CEA, CGA, DNA-Ploidy, Ploidy, DHEA, NSE, PAP, PSA,
PSADT, PSA
RT-PCR, Prolactin, Pyrilinks-D, Testosterone(T).
Stephen Strum, MD
commented on the use of CEA, CGA, NSE, PAP on a P2P post 3/9/2007:
"I
have advocated testing of the above markers but I see this
recommendation has been abused to where it is being routinely tested by
a number of physicians despite a validated GS of 6 or (3,4). I have
rarely (can't think of one case) seen elevations of these markers in
such instances, especially when the GS has been validated by an expert.
These markers are most useful in
THE CONTEXT of high Gleason scores such as (4,3) or higher (4,4), (4,5),
(5,4) or (5,5). These are NOT inexpensive tests & given the outrageous
costs of drugs, imaging, various treatments for PC, all of us must use
testing in a much more diligent manner."
CEA
(CarcinoEmbryonic Antigen). Is a cell-surface fetoprotein expressed
by many different tumor types, including poorly differentiated PC. Prior
to the advent of PSA elevated CEA was found in 30% of newly diagnosed
prostate cancers.
Moderately
elevated CEA concentrations have been found only in patients with either
"pure"or "predominantly" hormone insensitive disease
(without soft tissue lesions)
and particularly after suppression of hormone sensitive cell subpopulations.
CGA
(ChromoGranin A), there is a B, C, etc,. These "markers" are products
of the
tumor cell population and sometimes are clues as to the tumor taking
on an identity
that is associated more with certain clinical behavior, such as small cell
prostate cancer. Such small cell tumors grow faster, involve liver,
lung and lymph
nodes in unusual sites, frequently don't express much PSA and have lytic bone
lesions instead of dense blastic lesions, etc. CGA is an excellent marker for
neuroendocrine tumors, particularly nonfunctioning tumors, and the measurement
of CGA is also useful to detect prostatic carcinoma in patients whose PSA
is not elevated."
DNA-Ploidy
DNA (DeoxyriboNucleic Acid)is the basic biologically active chemical which
defines the physical development and growth of nearly all living organisms.
PLOIDY
is a term used to describe the number of sets of chromosomes in a cell. Tests performed
on biopsy samples are reported as: DIPLOID; having one complete set
of normally paired chromosomes, which is a normal amount of DNA. Diploid cancer
cells tend to grow slowly and respond well to hormone therapy, ANEUPLOID: having
an abnormal number of sets of chromosomes and Tetraploid which means having
two paired sets of chromosomes, which is twice as many as normal. Aneuploid
cancer cells tend not to respond well to hormone therapy.
DHEA
(DeHydroEpiAndrosterone)is an adrenal androgen. DHEA levels decline
with age,
yet prostate gland enlargement and cancers increase with age. It is
possible that
DHEA, being a weak androgen, can actually attach to and block testosterone or
DHT receptors on prostate tissue, thus preventing the influence by more
powerful androgens DHT
(DiHydroTestosterone) 5-alpha-dihydrotestosterone is the male hormone
which is
most active in the prostate. It is made when an enzyme (5-alpha reductase)
in the
prostate stimulates the transformation of testosterone to DHT. There
are reports
that DHT is as much as 4X more active in prostate cancer than Testosterone.
Proscar (finasteride) is considered a potent 5-alpha reductase inhibitor
and is often
prescribed as part of a complete androgen blocade (CAB).
NSE:
(Neuron-Specific Enolase) is a specific marker for neuroendocrine tumors which
express proteins or enzymes that are reflective of a de-differentiated tumor
cell population such as small cell prostate cancer. When both CGA and
NSE are
elevated the prognosis is considered poor.
PAP
(Prostatic Acid Phosphatase) is an enzyme measured in the blood whose
levels may
be elevated in patients with prostate cancer that has invaded or metastasized
elsewhere. PAP is not elevated unless the tumor has spread outside the
anatomic prostatic capsule. A persistently elevated serum PAP is considered
evidence of mets, but only 75% of patients with mets have an elevated
PAP. Serum PAP noted at the time of diagnosis of prostate cancer is
usually associated with extra-prostatic spread. In a study at the Johns
Hopkins University School of Medicine, 21 of 460 men or 4.6% had elevations
of PAP. Of those men fully evaluated evidence of extraprostatic disease
was documented in all. Positive bone
scans, extraprostatic extension of disease, PSA > 100, positive lymph
nodes and
positive seminal vesicles were found. Most of the above patients with increased
PAP's (17 of 21) had abnormal DRE's consistent with disease outside
of the
prostate or PSA's > 100. Therefore, in these patients the PAP was
not that helpful.
In the remaining 4 patients, the PAP was helpful in directing treatment towards
systemic therapy as opposed to local therapy. A PAP determination as part
of the initial staging evaluation is still reasonable. In addition,
in some patients
PSA may be normal or zero while the PAP is elevated proving the PAP
to be
the only remaining biologic marker that can be followed.
PSA
(Prostate Specific Antigen)is a protein secreted by the epithelial cells
of the prostate gland including cancer cells. An elevated level in the
blood indicates an abnormal condition of the prostate gland, either
benign or malignant. PSA is used to detect potential problems in the
prostate gland and to follow the progress of treatment. PSA is currently
used as a specific diagnostic marker for the early detection of prostate
cancer and to separate patients with tumors from those without tumors.
Age
- related PSA "cutoff" values for screening. An earlier version
of this allowed PSA values to 4.5 (60s) and 6.5 (70s). Further
refinement of this now gives:
40-49
up to 2.5 ng/ml (nanograms per milliliter)
50-59
up to 3.5
60 + up to 4.0.
Following a radical prostatectomy, the PSA should
be 'undetectable.'
Free
PSA analysis sometimes called "PSA-II"( Prostate-Specific
Antigen type II ) reports
the percentage of free-PSA to total-PSA (total-PSA = free-PSA + bound-PSA)
and is helpful for screening purposes when PSA values are above the normal
threshold for an age group and less than 10; one study showed that men with
PSA II > 25% had no PCa; those with < 10% were likely to have
PCa.
PSADT
(PSA Doubling Time) has been evaluated in patients with a rising PSA
after local
treatment with either RP or RT. In these settings PSADT has been shown
to be
significantly shorter in those patients who developed metastases than
in those who
did not develop metastatic disease. If the PSADT is < 10 months there
is a high
probability of metastatic disease. Patients post-RP with this finding
would not
be good candidates for local RT; however patients with a long PSADT
would be such
candidates. Patients post-RT with a short PSADT have a high likelihood
of metastatic
disease whereas those with a long PSADT might be candidates for salvage
cryosurgery.
PSA
RT-PCR: PSA (Reverse Transcriptase-Polymerase Chain Reaction)is a blood
test that
detects micrometastatic cells circulating in the blood stream; may be
useful as
a screening tool to help avoid unnecessary invasive treatments (RP,
RT, etc.) on
patients with metastasized Pca, although not FDA approved it is available
at locations
where FDA approved clinical trials of the test are being done.
Prolactin
(PRL) is a trophic hormone produced by the pituitary which increases androgen
receptors and increases sensitivity to androgens. Prolactin modulates prostatic
androgen uptake, affects its intracellular metabolism and utilization, and
thereby promotes differentiation, growth and secretory function of the prostate.
Many but not all men treated with hormone manipulations develop elevated prolactin
levels and men who develop hyperprolactinemia during estrogen, diethylstilbestrol,
cyproterone or estramustine treatment have been reported to have
a much higher rate of disease progression and death from prostate cancer.
It has
been theorized that prolonged prolactin stimulation from long-term hormone therapy
could play role in the onset of androgen resistant tumors.
Pyrilinks-D
is a laboratory test that measures deoxypridinoline (Dpd), a specific marker
of bone resorption(loss), which is excreted unmetabolized in urine.
It can be
used to support the decision to initiate antiresorptive therapy and
track changes
in bone resorption rates in response to therapy. If
Dpd levels are higher than 5.4 in "men", the patient is experiencing accelerated
bone resorption and may be at increased risk of bone loss. The test is
usually run to establish a base line and then at 3 to 6 month intervals
to monitor
therapy.
Testosterone
(T) is the male hormone or androgen which comprises most of the androgens
in a man's body; chiefly produced by the testicles; may be produced
in tissues
from precursors such as androstenedione; T is essential to complete
male sexual
function and fertility.
Since there are different ways of reporting
testosterone, it is important to give the units the testosterone is
measured in. There is ng/dl and there is nM/Liter. nM/L x 28.8 = ng/dl.
Or, you can multiple ng/dl by 0.0347 to get nM/L. A castrate
testosterone of < 20 ng/dl is equivalent to a castrate testosterone in
nM/L at < 0.69. See also the FAQ section of
this website.
Harry
Pinchot (updated by H.Hansen 9 March 2007)
