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UPM3 - A diagnostic urine
test with greater accuracy for cancer detection than PSA
(April 2006)
The “Achilles’ heel” of
the venerable PSA test is its low specificity for prostate cancer
detection, ~25% to 35%, when used for screening and in the work-up of
suspicious palpable abnormalities, allowing critics to charge an
unacceptably high rate of “unnecessary biopsies”. An excellent, and
concise, discussion of the detection efficiency of PSA for initial and
repeat biopsies is: “Prostate biopsy: who, how and when. An Update” by Bob
Djavan et al., Canadian Journal of Urology; 12(Supplement 1);February
2005. They report data from the European Prostate Cancer Detection “study
of 1051 men with a total PSA of between 4 ng/mL and 10 ng/mL who underwent
a 12 core biopsy (two in the transitional zone). Those with negative
biopsies were rebiopsed at 6 weeks, and, if negative, then biopsied again
a third and fourth time at 8 week intervals. Results: “Cancer detection
rate on first, second, third and fourth biopsy was 22% (231/1051),
10%(83/820), 5% (36/737) and 4% (4/94).” Clearly there is room for
improvement!
The uPM3 offers such
improvement, and is discussed by Fred Saad, Canadian Journal of Urology
(see above): “UPM3: review of a new molecular diagnostic urine test for
prostate cancer”. “In a large multi-center study of 517 cases the overall
sensitivity was 66% with a specificity of 89%. The positive (PPV)
predictive values for the uPM3 test was 75% compared to 38% for a serum
PSA cutoff of 4 ng/mL” - yielding a two-fold better accuracy. For PSA
cutoff of 2.5 to 4 ng/mL the comparative accuracy was 81% versus 43% for
PSA. In the PSA range of < 4 ng/mL: sensitivity, 74%, specificity, 95%.
The test focuses on
exfolliated cells loosened by a “vigorous” prostatic massage, 30 seconds
for each lobe, and swept from the urethra into the urinary stream. The key
test target is PCA3 mRNA identifying the presence of cells carrying the
PCA3 gene, “one of the most prostate cancer specific genes described to
date, with overexpression in 95% of cancers tested and a median 66-fold
up-regulation compared to adjacent non-neoplastic prostate tissue”. The
simultaneous presence of PSA and target PCA3 mRNA assures
that the cells in question are of prostate origin.
The test kit is available
from the Bostwick Laboratories (webkeeper@bostwicklboratories.com) and
costs about $450. The marketing specialist in Seattle is Bonnie Scott (
206-853-2573 ). Scientific questions can be addressed to Junqi Qian, MD,
Director of Molecular Diagnostics, (jquin@bostswicklaborotories;
804-288-6564), who informed me that in June, 2006, the next generation of
the test (“PCA3”) will be available.
The Djavan article
discusses currently available methods to improve the detection rate for
PSA prompted biopsies. The Vienna nomogram (J Urol. 2005 Oct;174(4 Pt
1):1256-60) offers a strategy for “defining the optimal number of cores
based on patient age and prostate volume” which raised the detection rate
to 36.7% on the initial biopsy “compared with 22% on the first and 10% on
the repeat biopsy in the control group” of their 1051 man study. Also
discussed was a PowerDoppler-TRUS imaging technique which “excluded
prostate cancer in 89.7% (52/58) and 94.4% (17/18) of patients on the
first and repeat biopsies.
How might the uPM3 test
be best integrated into clinical practice? “Very discretely” might be the
answer by many physicians. At $450 a pop there may be a substantial number
of instances where uMP3 test would be an expensive “add on” considering
that an experienced clinician could likely make a sound decision based
upon a sufficiently adverse constellation of findings combining a
worrisome palpable abnormality, a low percent free PSA, a PSA level
concerningly above the appropriate level for a man’s age group, or a PSA
rise of more than .75 ng/mL per year. Yet, there may well be many
clinically marginal situations in which an initial biopsy might be
conservatively “on hold” where the uMP3 test would be clearly helpful.
It is possible that at
first this test may be most useful to help decide whom to rebiopsy after
an initial negative biopsy, but in which the presentation remains
suspicious for cancer. In this setting of one or more negative biopsies
the “uPM3 had a 74% sensitivity and a 87% specificity corresponding to a
negative predictive value of 87% and a positive predictive value of 74%
(from Saad). Similarly the uPM3 may be helpful in cases where HGPIN was
found in several foci and rebiopsy is under consideration.
Bottom Line:
The uPM3 test is available for thoughtful integration into clinical
practice and has excellent sensitivity and specificity for cancer
detection.
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