Complexed PSA Test More Accurate Than Traditional
PSA Test in Detecting Prostate Cancer
Study Indicates cPSA Test More Predictive of Cancer,
Results in Fewer False Diagnoses and Unnecessary Biopsies
PSA Rising - October 11, 2003: A new study on detection of prostate cancer
finds that measurement of complexed PSA (cPSA, or serum concentration of complexed
prostate specific antigen) is more accurate than the total PSA (tPSA)
test currently used by most physicians.
The study, published in the November
issue of The Journal of Urology, showed that the cPSA test is more predictive
of prostate cancer and results in fewer false diagnoses and unnecessary biopsies
compared to the traditional tPSA test.
"These findings are important because they suggest that use of the cPSA test can decrease the number of unnecessary prostate cancer biopsies particularly if a lower PSA threshold is utilized. This approach will not only save healthcare expenditures but will also spare many men the discomfort and anxiety associated with biopsy procedures," said investigator Richard Babaian, M.D., from MD Anderson Cancer Center. "In view of these findings, physicians and patients should consider using the cPSA test when screening for prostate cancer."
PSA, a protein produced in the prostate, has proven to
be an extremely useful marker for early detection of prostate cancer and in
checking for disease progression and the effects of treatment.
PSA serum levels of 4.0 ng/ml or less are usually considered normal; higher
levels (4 to 10 ng/ml or higher) are often found in men with prostate cancer.
However, current PSA testing generates up to 60 percent "false positive" diagnoses
because PSA levels can also increase due to enlargement of the prostate, a
non-cancerous condition increasingly common as men get older, as well as acute
infections of the prostate (prostatitis), and other factors.
On the other hand, testing can also generate "false negatives" because
a significant number of cases of prostate cancer have been found in men whose
PSA was "normal," between
2.5 to 4 ng/ml.(ii)
The ability of a test to detect cancer is defined as sensitivity;
the ability to detect those without cancer is defined as specificity. Sensitivity
can be increased by lowering the tPSA "cutoff" value at which a physician suspects cancer, but doing so will decrease specificity, since it will also increase the number of men suspected of cancer but who don't actually have it.
Therefore, much research has focused on ways to improve the accuracy of PSA
testing, i.e., to increase both sensitivity and specificity.
Some studies have
shown that the cPSA test is equivalent to the tPSA test while others have
shown it is better than tPSA. Other PSA tests include those that measure
free (vs. complexed) PSA and the percentage of tPSA comprised of free PSA and
Study and Findings
In this study, conducted at seven prostate cancer treatment centers, blood
samples were collected from 831 men who were about to undergo initial
prostate biopsy. The biopsies showed that 313 (37.5 percent) had prostate cancer.
Knowing which patients turned out actually to have prostate cancer, the
investigators compared the accuracy of the predictions of the cPSA and tPSA
tests. They found that cPSA was significantly more predictive of cancer than
tPSA, and provided an improvement in specificity (reduced false positives)
compared to tPSA. For example, for men whose tPSA levels were in range of 2
to 4 ng/ml (cPSA range 1.5 to 3.2 ng/ml), using a cutoff of 2.2 ng/ml for cPSA
and 2.5 ng/ml for tPSA resulted in both tests correctly identifying cancer
85 percent of the time, which is considered highly sensitive.
this 85 percent sensitivity level, the cPSA test correctly identified 35
percent of patients who did not have cancer, compared to 21.2 percent for the
tPSA test. So the cPSA test would have spared significantly more
men -- 14 percent -- who did not have cancer from undering an unnecessary
biopsy and the inconvenience and anxiety associated with that procedure.
"Urologists are increasingly looking at the lower range of PSA values to maximize the detection of prostate cancer," said Dr. Babaian. "Since this lower range also includes many men without cancer, the enhanced specificity of the cPSA test to detect those who are cancer free and avoid unnecessary biopsies is an important advantage over the standard tPSA test."
The investigators compared the predictive value of the tests in other ranges as well. For the range of 2 to 10 ng/ml tPSA (1.5 to 8.3 ng/ml for cPSA), the cutoffs of 3.37 ng/ml tPSA and 2.87ng/ml cPSA provided 85 percent sensitivity, but the cPSA test correctly identified 35 percent of patients who did not have cancer, compared to 29 percent with the tPSA test -- saving unnecessary biopsies in six percent more of the men without cancer, also statistically significant.
Other recent studies in Germany and Japan (see below) arrived at somewhat
different conclusions by comparing the array of tests available today. One
thing clear is, patients do have more chance today of receiving more
accurate tests for prostate cancer. Chances of avoiding
unnecessary biopsies while finding significant tumors are improving.
Prostate cancer is the second leading cause of male cancer death in the
U.S. The American Cancer Society estimates that 220,900 men will be diagnosed
with prostate cancer this year in the U.S., with 28,900 deaths attributable
to prostate cancer.
J Urol 2003; (Volume 170, November 2003) Complexed
PSA improves specificity for prostate cancer detection: results
of a prospective multicenter clinical trial. Partin AW, Brawer MK, Bartsch G, Hominger W, Taneja
S, Lepor H, Babaian RJ, Childs S, Stamey T, Fritsche HA, Sokoll
LK, Chan DW, Thiel RP, Cheli CD.
J Urol. 2003 Oct;170(4 Pt 1):1175-9. A
multicenter clinical trial on the use of complexed prostate specific antigen
in low prostate specific antigen concentrations. Lein M, Kwiatkowski M, Semjonow A, Luboldt HJ, Hammerer P, Stephan C, Klevecka V, Taymoorian K, Schnorr D, Recker F, Loening SA, Jung K.
Department of Urology, University Hospital Charite, Humboldt University Berlin, Germany.
Int J Urol. 2003 Apr;10(4):201-6. Predictors
of prostate cancer on repeat prostatic biopsy in men with serum total prostate-specific
antigen between 4.1 and 10 ng/mL.
Okegawa T, Kinjo M, Ohta M, Miura I, Horie S, Nutahara K, Higashihara E.Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan
Urology. 2002 Oct;60(4 Suppl 1):31-5. Complexed
prostate-specific antigen for early detection of prostate cancer in men with
serum prostate-specific antigen levels of 2 to 4 nanograms per milliliter. Horninger W, Cheli CD, Babaian RJ, Fritsche HA, Lepor H, Taneja SS, Childs
S, Stamey TA, Sokoll LJ, Chan DW, Brawer MK, Partin AW, Bartsch G. Department of Urology, University of Innsbruck, Austria
JAMA. 1997 May 14; 277(18):1452-5. Enhancement of specificity
with free PSA measurements. Prostate cancer detection in men with serum PSA
concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Catalona
WJ, Smith DS, Ornstein DK
Edited by J. Strax. Updated 2003-10-11