SWOG Cancer Research Network, an international cancer clinical trials
group funded by the National Cancer Institute (NCI), part of the
National Institutes of Health, opened the PCPT for enrollment 25 years
ago. The PCPT enrolled 18,882 men from 1993 to 1997, making it one of
the largest prostate cancer clinical trials ever conducted. New results,
which reported participant deaths over two decades, show that
finasteride has the lasting effect of reducing prostate cancer risk.
Results also eliminate concerns over initial findings of a possible risk
of more aggressive cancers with finasteride use.
Finasteride powder
is safe, inexpensive, and effective as a preventive strategy for
prostate cancer,” said Ian Thompson, Jr, MD, principal investigator of
the PCPT for SWOG. “Doctors should share these results with men who get
regular prostate-specific antigen tests that screen for the presence of
prostate cancer. The drug will have its greatest effect in this group of
men.”
Thompson is chair of SWOG’s genitourinary cancer committee and serves as
president of CHRISTUS Santa Rosa Hospital - Medical Center in San
Antonio, Texas and as emeritus professor at the University of Texas
Health Science Center. Along with SWOG biostatisticians Catherine
Tangen, DrPH, and Phyllis Goodman, MS, of Fred Hutchinson Cancer
Research Center, Thompson sought to determine whether the increased
number of high-grade cancers detected through the PCPT years ago would
result in more prostate cancer deaths over time.
SWOG published the first PCPT results in 2003. Investigators reported a
significant, positive result: finasteride reduced prostate cancer risk
by 25 percent. But the study also cast a shadow on the drug, the first
5-alpha-reductase inhibitor which targets and blocks the action of
androgens like testosterone and is commonly used to treat lower urinary
tract problems in men and also male pattern baldness. The results showed
that finasteride increased the number of high-grade prostate cancers – a
finding that resulted in a drug label warning posted by the U.S. Food
and Drug Administration. That warning persists to this day.
So is finasteride safe in the long run? Thompson, Tangen, and Goodman
matched participants to the National Death Index, a centralized database
of death record information managed by the U.S. Centers for Disease
Control and Prevention. This analysis allowed the SWOG team to determine
if a trial participant had died, and if so, the cause of death. With
almost 300,000 person-years of follow-up and a median follow-up of 18.4
years, they found 42 deaths due to prostate cancer on the finasteride
arm and 56 on the placebo arm. Thus, there was no statistically
significant increased risk of prostate cancer death with finasteride.
In the NEJM letter, the team notes that a cheap, reliable prostate
cancer prevention drug will have a big impact on public health. Due to a
rise in screening for the disease, prostate cancer diagnoses are on the
rise, with the American Cancer Society estimating that 164,690 American
men would be diagnosed in 2018. While many of these cancers will be
slow-growing, and not life-threatening, they are still often treated
with surgery and radiation, resulting in common complications such as
impotence and incontinence.
“There are significant negative consequences to patients’ health and
quality of life that can result from prostate cancer treatment, as well
as to their finances and their peace of mind,” Thompson said. “If we can
save people from surgeries, and scores of examinations and tests, and
spare them from living for years with fear, we should. The best-case
scenario for patients is prevention, and this trial has found an
inexpensive medication that gets us there.”
The NCI and the National Institutes of Health funded the study through grants CA037429 and CA182883.
Other members of the SWOG study team include Amy K. Darke, MS, of Fred
Hutch; M. Scott Lucia, MD of University of Colorado, Denver; Leslie G.
Ford, MD, of the Division of Cancer Prevention at the NCI; Lori M.
Minasian, MD, of the Division of Cancer Prevention at the NCI; Howard L.
Parnes, MD, of the Division of Cancer Prevention at the NCI; and
Michael L. LeBlanc, PhD, of Fred Hutch.
