|
Prostate Cancer Prevention Trial - Final Results At Seven Years
In July the NEJM published the final results of a seven year trial
comparing 4369 men taking 5 mg finasteride with 4692 on a placebo. The
study hypothesis: 1) by interrupting the enzyme 5 alfa-reductase,
finasteride decreases the conversion of testosterone to the more potent
dihydrotestosterone (DHT), a conversion which mainly takes place in the
stromal cells surrounding normal prostate epithelium; 2) less DHT is then
presented to the nearby epithelial cells thereby decreasing their
intracellular DHT by 90%; 3) higher loads of DHT are thought to lead to an
increase in the development of prostate cancer; 4) ergo: finasteride will
decrease the prevalence of PC. [Prevalence: The total number of cases of a
disease in a given population at a given time]. And it did - by 24.8%
(18.4% developed cancer in the finasteride group v. 24.4%, placebo). The
eligibility criteria for trial participation were age >55, apparent good
health, a normal digital prostate exam, and a PSA < 3 ng/ml. As expected
finasteride effected a comparative decrease in urinary symptoms, but was
associated with significantly more erectile dysfunction, loss of libido,
and gynecomastia.
A thoughtful editorial by Scardino, however, raises some important issues.
First, he notes that the accepted expected incidence of the diagnosis of
cancer in this age group is 6% when a diagnosis results from customary
clinical practice indications for biopsy - and he views both the 18.4% and
24.4% values as excessive and requiring explanation. [Scardino's usage of
"incidence" is to be differentiated from "prevalence" because of the
study's policy of performing biopsies for "no cause"] The NEJM study
design did not require a prostate biopsy at entry. Presumably the number
of undetected cancers in the men at entry was equal in the groups.
Biopsies were performed in the course of the trial if a PSA rose above 4
ng/ml (2 ng/ml for men on finasteride) or clinical findings were abnormal.
Participants who did not exhibit these indications for biopsy were asked
to undergo biopsy at the end of their seven years - so called biopsies for
"no cause". Examination of the study statistics reveals that in the
finasteride group 9.9% (435/4368 = 9.9%) were diagnosed with PC as a
result of a PSA rise above 4 ng/ml or clinical indications; and in the
placebo group 12.1% (571/4692 = 12.1%) were diagnosed as result of meeting
these clinical indications. In the category of "biopsy without cause" PC
was diagnosed in 8.4% (368/4368 = 8.4%) in the finasteride group v 12.2%
(576/4692=12.2%) for placebo. Scardino notes that autopsy studies on
asymptomatic men >55 years old have revealed prostate cancer in 30 - 40%,
and the NEJM study may have tapped into this subclinical pool of prostate
cancer, thus contributing to an explanation of the high rate of PC
detection in this study. Scardino discusses this issue of possible "overdiagnosis"
of insignificant cancers - cancers that might not have clinical
significance during a man's lifetime - that arises from the study schema
that includes "no cause" biopsies.
Probably the most worrisome finding, however, was that cancers with
Gleason sums >7 were found in 6.4% of the finasteride group v. 5.1% for
untreated men. Scardino's concerns are sufficient to make him doubtful
that finasteride will be widely used for prostate cancer prevention. If
preventive treatment is offered, a full discussion of the details is
required.
Bottom Line: Finasteride treatment decreases the prevalence of
prostate cancer, but significant reservations exist about the usage of
finasteride in prostate cancer prevention.
«
Back to Article List |
