- Risk of prostate cancer related to sex hormone levels - A report
by researchers at Harvard University, Boston, and Northwestern
University, Chicago, implicated high testosterone levels and low
levels of serum hormone binding proteins and estrogen, as being
associated with increased risk of prostate cancer. The study,
published in the August 21, 1996 issue of the Journal of the National
Cancer Institute, used plasma samples collected from participants
in the Physicians' Health Study in 1982, among whom 22 had
developed prostate cancer by March 1992. (Gann, JNCI 88:1118,
1996)
Editor's Comment: - A stimulatory effect of testosterone on the
growth of prostate cancer has been known for some time. Benign
prostatic hypertrophy or enlargement (BPH) also appears to be
stimulated by testosterone. Low levels of the sex hormone
binding protein (SHBG) will leave more testosterone free, and
since it is the free hormone which is active, a low SHBG
concentration is equivalent to an increase in testosterone level.
The result for the female hormone estradiol is unexpected, since
high estradiol levels decrease BPH. Perhaps as the authors
suggest, BPH and prostate cancer represent different responses to
hormone. They are certainly associated with changes in different
regions of the prostate - the central and peripheral zones,
respectively.
- Looking closely at prostate cancer statistics - Over the past 30
years there has been an increase in incidence of prostate cancer
paralleled by a similar increase in survival rates. However,
there is no real evidence over this time of a similar degree of
improvement in curative treatment. What is going on here? A
Swedish study, published in the September 4, 1996 issue of the Journal
of the National Cancer Institute, looked at the statistics for
all prostate cancer cases (80,901 in all) diagnosed in Sweden
between 1960 and 1988. The researchers documented a steady
improvement in survival over time. Ten-year survival rates, for
example, increased from 29% among patients diagnosed in 1960-1964
to 45% among those diagnosed 1975-1979. Throughout the time
period 1874-1987, there were 74% and 132% increases in grades 1
and 2 tumors among new cases, respectively, while the numbers of
more advanced grade 3 tumors remained unchanged. The authors
attributed the results to detection of early, essentially non-lethal
tumors, and calculated that at least one third of the
patients diagnosed between 1980 and 1984 had such tumors.
(Helgesen, JNCI 88:1216, 1996)
Editor's Comment: - These findings relate to a controversial and
recurrent issue in the US - what to do about small prostate
cancers that are not going to kill the patient. It is true that
the course the cancer will eventually take cannot be known for
sure, since there are no tests to determine which will progress
and which will stay limited and not become a threat to life.
Much research is underway to develop such tests. An example of
this can be seen in the September 15, 1996 issue of Cancer Research
(Mashal, Cancer Res 56:4159, 1996) where it was concluded that
the ratio of the measurement (by staining) of two indices of
cellular proliferation - cyclins and Ki-67 - appears to give good
prognostic information for localized prostate cancer. Use of
such multiple and complex tests may be the answer. In the
prevailing circumstances, however, different patients and their
physicians have no alternative but to chose between two different
courses of action - watchful waiting or preventive surgery. The
Swedish researchers attribute the increased incidence of small
tumors to increased use of digital rectal examinations and of
TURP, the transurethral surgical treatment for benign enlargement
of the prostate. To this should be added increasing reliance on
PSA measurements as a screening tool for early prostate cancer.
- PSA as a screen for prostate cancer, a feasibility study from
Finland - PSA measurements are being increasingly used to
identify prostate cancer that is still confined to the organ and
so treatable. To be useful, a screening test must be readily
accepted by the population that is at risk. So far, however, no
studies have been done to assess how acceptable the technique of
PSA measurement might be for randomized screening of large
populations. The report of a pilot Finnish study on this issue
appeared in the August, 1996 issue of the British Journal of Cancer.
In a random invited sample of 300 men, the participation rate was
found to be quite high at 77%. Serum PSA was higher than the
standard cut-off point of 4 nanograms/milliliter in 25 of the
men, of whom 6 were found to have cancer by digital examination,
transrectal ultrasound, and biopsies. This represented a
detection rate of 2.6% and positive predictive value of 24% for
PSA measurements. Five of the cancers were localized. The false
positive rate of 8% was reduced to 3% by using the ratio of free
to total PSA (cut-off at 0.2), a ratio that has been suggested as
being more specific than total PSA, but at the cost of missing
one of the cancers. (Auvinen, Brit J Cancer 74:568, 1996)
Editor's Comment: - Widespread PSA measurements are being done
already in an informal mass screen for prostate cancer, but it is
still necessary to do some of the type of work done in this study
to confirm the reliability and predictive value of PSA, and to
find out whether men will participate at the required level.
However, as mentioned before in this and other issues of the
CancerWeb Report, screening does not resolve the issue of what to
do with small cancers once they are identified. In fact it
complicates the issue by identifying large numbers of men with
very early-stage cancers. Obviously we need what is not now
available - another test that can be applied widely and easily to
identify the cancers that are likely to become a threat to health
and life. The alternative is to operate on or irradiate everyone
with positive findings. This may prevent further development of
cancer, but it will also produce such unwanted complications as
incontinence and impotence in many men whose disease may never
otherwise have caused them any problem.
- A report on benign prostatic hypertrophy (BPH) causes confusion
for the prostate cancer prevention study - A report in the August
22, 1996 issue of the New England Journal of Medicine (Lepor, p.
533) has caused some confusion for those enrolled in a study of
Proscar (finasteride) as a potential preventive treatment for
prostate cancer. The BPH study confirmed what in many ways is
obvious, a medication that shrinks the prostate will only work if
the organ is enlarged. Proscar inhibits the enzyme that produces
active androgen thus reducing the stimulatory effect of androgen
on prostate growth and causing the organ to shrink. However,
such prostate problems as obstruction of urine flow, do not
always result directly from an enlarged prostate. They more
often reflect tension in the muscular layer of the prostate which
squeezes the bladder outlet and urethra, reducing urine outflow.
In such cases, drugs like the muscle relaxant terazosin will
relieve the problem, whereas the shrinking effect of Proscar on
the gland due to its antiandrogenic action will have little
effect on the symptoms unless the prostate is much enlarged.
Unfortunately the report was a major news item, and presented in
the media as a demonstration that Proscar is valueless. It was
not pointed out that the men in this study did not have very
large prostates, a critical factor for Proscar to be active. In
the case of the ongoing $60 million study of Proscar as a
preventive for prostate cancer, the objective is not to relax the
muscle layer but to take advantage of the antiandrogenic effect,
which should slow or prevent the growth of precancerous tissue
and early cancer in the organ.
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