cancer diagnosis clinical practice guidelines:
Every man should have an annual PSA and DRE starting at forty years of age. Men
at risk due to a family history of prostate cancer (brothers, fathers),1-3
men with a family history of breast cancer (mothers, sisters, aunts)1,4-6
and African-American men should begin annual screening at age 35.
of 2.0 and over at any age should be investigated to rule out prostate cancer
A first step in investigation of a PSA elevated at 2.0 or above
should be a free PSA percentage test.
· A free PSA percentage
of over 25% is associated with a low risk of prostate cancer.
free PSA percentage of under 15% is associated with a higher risk of prostate
benign cause of an elevated PSA and a correspondingly low free PSA percentage
could be prostatitis. Four to six weeks of Cipro or similar antibiotic should
be prescribed prior to recommending a biopsy if prostatitis symptoms are noted
and/or if expressed prostatic secretions (EPS) are consistent with
· prostatitis. At the end of the Cipro therapy, a repeat PSA determination
should be made. If there is significant lowering of the PSA, an element of prostatitis
is most likely present. The PSA value after antibiotic therapy will more aptly
reflect the status of the patient in the situation where PC is subsequently established.
· BPH (benign prostate hyperplasia) does not cause a low free
PSA percentage. It may cause an elevated PSA, however. Therefore, in the case
of an elevated PSA but a high free PSA percentage (equal to or greater than 25%),
an estimate of gland volume by DRE or via transrectal ultrasound of the prostate
may reveal findings consistent with a diagnosis of BPH. A general rule of thumb
is that an accurate gland volume (best determined by transrectal ultrasound of
the prostate) x 0.066 will equal the amount of benign-related PSA. Therefore,
assuming only the presence of BPH, a 60-gram or 60 cubic centimeter prostate is
entitled to secrete approximately 3.96 ng of PSA into the blood.
sampling for PSA determinations, done at least three months apart, and by the
same laboratory using the same testing procedure, are necessary to establish PSA
velocity (PSAV) and PSA doubling time (PSADT). The validity of such determinations
is increased if such testing involves at least three determinations over an 18
month span of time. However, a progressive and serial increase in PSA values should
raise flags of concern that prostate cancer is present and a greater degree of
vigilance is mandatory.
· A PSAV that exceeds 0.75 ng/ml/yr is
associated with a higher probability of PC.8
· A PSADT of less than 12 years is associated with a higher probability
PSA's that bounce up and down are more indicative of a benign
process than a malignant process.
A PSA that shows a persistent rise
over time, particularly three consecutive rises, three months apart is suspicious
for PC regardless of the level of the PSA. As mentioned above, gland volume in
cubic centimeters (cc) multiplied by 0.066 yields the amount of PSA produced by
the benign-related epithelial cell population of prostate cells. Any amount of
PSA in excess of this should be considered to be produced by a malignant process
until proven otherwise.
an additional new screening tool has become available. Bostwick Labs now offers
the PCA3PlusTM test, the successor to the uPM3 test introduced in 2004 as the
first urine-based genetic test for prostate cancer. The test is based on PCA3,
a specific gene that is profusely expressed in prostate cancer tissue and in urine
after prostatic massage. On average, the incidence is 34 times greater in malignant
prostate tissue as opposed to benign prostate tissue. No other human tissues have
ever been shown to produce PCA3. The PCA3PlusTM test predicts prostate cancer
with a sensitivity of 95.7%. Therefore, after an elevated PSA, further investigations
are possible, which reasonably might include PCA3PlusTM testing to enhance the
accuracy of diagnosis. Systematic biopsies of the prostate under ultrasound guidance,
however, must be considered mandatory when clinical and/or laboratory findings
suggest the possibility of prostate cancer.
An approach using biological
detection techniques such as those described above would eliminate advanced presentations
of PC. Annual screening in this manner presents us with an opportunity to detect
localized PC in over 95% of men.9 Such statistics offer
an outstanding chance for a curative approach to this disease.
involving these profiling techniques allows the patient-physician team to discern
the very slow growing (indolent) presentations of PC that may be monitored using
watchful waiting as opposed to the standard PC cases for which local treatments
typically result in long term biological non-evidence of disease. Most importantly,
attention to PSA kinetics accomplished by monitoring the PSA and PSA derivatives
such as free PSA percentage, PSADT, PSAV and other calculations, should result
in an almost total disappearance of highly aggressive presentations of PC. It
is the latter that is associated with rapidly progressive disease and fatalities.
These opposite extremes in the clinico-pathological nature of PC, i.e.
the indolent "pussycats" variants versus the aggressive "tigers" ones, are important
to differentiate due to the highly different evaluation and management recommendations
advised for each circumstance.
Indolent versus Aggressive PC ("Pussycats"
Pussycats in general, have low PSA values (under
10) and long doubling times (greater than 24 months and often 48 months or longer),
as well as low PSA velocities (0.75 ng/ml/yr ± 10%). . If a biopsy is done on
a patient with a PSA that is under 10, the Gleason score often turns out to be
(3,3). Depending on the calculated tumor volume, clinical stage, PSA doubling
time, and other factors, these objectified biologic parameters may allow many
such patients to be candidates for objectified observation ("watchful waiting").
Of course, these patients are also candidates for any of the currently FDA-approved
local therapies. Patients who choose to monitor their illness rather than seek
immediate local therapy must be cognizant of the significance of change over time,
or trend. They need to be aware that if manifestations of disease progression
become evident, reevaluation of their situation is warranted. In such circumstances,
consideration must be made for some form of local treatment-before the window
of opportunity for successful local therapy is lost.
Tigers in general,
have high PSA's (over 10) OR very low PSA's associated with very aggressive, high
Gleason score [(4,3), (4,4), (4,5), (5,4), (5,5)] cancers. These are very dangerous
because they often escape investigation for long periods of time since the PSA's
appear to be in the so-called normal range. Investigating all PSA's 2.0 and over
will help to catch these prostate cancers while they are still organ-confined
and treatable with local therapies. The probability of spotting these low PSA/high
Gleason score cancers is enhanced if patients and doctors monitor PSA levels over
time to note any persistent increases even if the PSA is very low. High Gleason
score cancers often have reverted to such a primitive state that they no longer
secrete PSA into the blood. Checking the serum for elevations in other markers
such as CGA (Chromogranin A), NSE (Neuron Specific Enolase), CEA (Carcino-Embryonic
Antigen) and PAP (Prostatic Acid Phosphatase) is important to discern PC activity
secondary to de-differentiated tumor cell populations. Therefore, in cases such
as this, the normal guidelines for PSA velocity and doubling time may not be applicable.However,
the concept of slope or trend in a biomarker of disease activity remains valid,
and any biomarker elevation should be tracked at regular intervals to determine
the presence of abnormal growth of primitive tumor cell clones.
If we scientifically observe the biological manifestations of prostate health
or disease, we can detect PC at a time when currently available therapies are
most likely to cure the most common malignancy facing man. If we ignore these
biological communications that are red flags to alert us to the presence of a
threat to our life, a vital opportunity to change the course of an illness is
missed. The loss of life, productivity, and the extreme costs to the health care
system - all of which result from a late-stage diagnosis of this disease - should
provide impetus for all of us to be proactive when it comes to an early diagnosis
of a malignant condition. This fundamental concept has been heralded for many
malignances, such as cancer of the cervix, lung cancer, colorectal malignancy
and breast cancer. When will we make the same connection when it comes to men
with PC?10 Aren't the almost 300,000 American lives lost
each decade too great a price to pay?
RESOURCES FOR PHYSICIANS AND
On the Web:
The Prostate Cancer Research Institute
(PCRI) web site at http://www.pcri.org
. This site has a wealth of information including the Prostate Cancer Address
Book, which lists expert prostate cancer physicians, software tools, and articles
and downloadable issues of the publication PCRI INSIGHTS.
INTERNATIONAL - http://www.ustoo.org/.
This is the world's largest independent, charitable network of education and support
groups for men with prostate cancer and their families.
"A Primer on Prostate Cancer, The Empowered Patient's Guide" by Stephen B. Strum,
MD, FACP and Donna Pogliano, Second Edition, copyright 2005, now also available
in the German language. The Primer is available at web booksellers such as www.amazon.com,
www.lefprostate.org. It can also
be ordered through the Life Extension Foundation (1-866-820-7457) and at Barnes
& Noble, Borders, and other fine bookstores everywhere. This is an in-depth guide
about prostate cancer that presents a comprehensive approach to the diagnosis,
evaluation and selection of therapies currently available to the prostate cancer
patient. It consists of 368 pages of fully indexed text with 168 full color graphics
to enhance a clear understanding of prostate cancer. It is intended to bring the
patient-partner-physician team involved with prostate cancer from a basic understanding
of this disease to a highly sophisticated level of understanding.
together, we can achieve vast inroads into the diagnosis, evaluation and treatment
of this illness.
JR, Parker AS, Putnam SD, et al: Family history and prostate cancer risk in a
population-based cohort of Iowa men. Cancer Epidemiol Biomarkers Prev 8:53-60,
2. Hayes RB, Liff JM, Pottern LM, et al: Prostate cancer risk in U.S.
blacks and whites with a family history of cancer. Int J Cancer 60:361-4, 1995.
3. Isaacs SD, Kiemeney LA, Baffoe-Bonnie A, et al: Risk of cancer in relatives
of prostate cancer probands. J Natl Cancer Inst 87:991-6, 1995.
Bennett KE, Howell A, Evans DG, et al: A follow-up study of breast and other cancers
in families of an unselected series of breast cancer patients. Br J Cancer 86:718-22,
5. Ford D, Easton DF, Bishop DT, et al: Risks of cancer in BRCA1-mutation
carriers. Breast Cancer Linkage Consortium. Lancet 343:692-5, 1994.
DE, Easton DF, Cannon-Albright LA, et al: Systematic population-based assessment
of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst
7. Ito K, Yamamoto T, Ohi M, et al: Free/total
PSA ratio is a powerful predictor of future prostate cancer morbidity in men with
initial PSA levels of 4.1 to 10.0 ng/mL. Urology 61:760-4, 2003.
Ito K, Yamamoto T, Ohi M, et al: Usefulness of prostate-specific antigen velocity
in screening for prostate cancer. Int J Urol 9:316-21, 2002.
Labrie F, Candas B, Cusan L, et al: Diagnosis of advanced or noncurable prostate
cancer can be practically eliminated by prostate-specific antigen. Urology 47:212-7,
10. Labrie F, Candas B, Dupont A, et al: Screening
decreases prostate cancer death: first analysis of the 1988 Quebec prospective
randomized controlled trial. Prostate 38:83-91, 1999.