The
information in this column is intended for informational
purposes only, and does not constitute medical advice or
recommendations by the author. Please consult with your
physician before making any lifestyle or medication changes, or if you
have any other concerns regarding your health.
VITAMIN D & PROSTATE
CANCER RISK
I have reported
on previous clinical research studies suggesting that increased levels
of
Vitamin D in the blood may be associated with a lower risk of certain
cancers
(and colorectal and prostate cancer, in particular).
I have also previously summarized my view
that the epidemiological data supporting a cancer-protective effect for
Vitamin
D is relatively weak, and that the available body of research on this
topic
contains the findings of multiple studies that appear to contradict
each
other. Now, a newly
reported study in
the Journal of the National Cancer
Institute adds to this body of clinical research literature
on Vitamin D
and prostate cancer prevention.
This
research was
performed by investigators from the National Cancer Institute, the University of Washington,
and the University
of Alabama. This research study was
part of a larger
study known as the Prostate, Lung, Colorectal, and Ovarian (PLCO)
Cancer
Screening Study. This
study included 749
patients who developed prostate cancer during the course of the study,
as well
as 781 control patients who did not develop prostate cancer (all male
patients
who participated in this study underwent annual screening for evidence
of prostate
cancer). At the
onset of this clinical
research trial, and before any of these patients were diagnosed with
prostate
cancer, blood was analyzed for various factors, including Vitamin D
levels. Unfortunately,
the results of
this study were somewhat disappointing in view of previously published
studies
showing that high levels of Vitamin D in the blood appeared to be
associated
with a lower risk of prostate cancer.
In
this study,
higher levels of Vitamin D in the blood did not appear to have any
protective
effect, whatsoever, against developing prostate cancer.
In fact, on the contrary, among those
patients diagnosed with prostate cancer during this clinical research
trial,
higher levels of Vitamin D in the blood appeared to be mildly
associated with
more aggressive cancers.
The
findings of
this rather large, prospective clinical trial will be disappointing to
those
who have believed that increased levels of Vitamin D in the blood might
protect
against the onset of prostate cancer.
While Vitamin D has been shown to reduce prostate cancer
cell growth in
laboratory studies, the results of human studies have been less
compelling and
less consistent.
Although
the
findings of this study suggests that very high levels of Vitamin D in
the blood
of patients already diagnosed with prostate cancer might be associated
with
more aggressive tumors, the correlation between blood levels of Vitamin
D and
tumor aggressiveness was not uniform, suggesting that this observation
has not
been definitively proven by the data derived from this study. Another limitation of this
particular study
is that Vitamin D levels in the blood were only measured a single time
during
the course of this study (at the beginning of the study). It is, therefore, not
possible to know whether
or not Vitamin D levels might have fluctuated considerably during the
period of
several years when this study was being carried out.
According
to
American Cancer Society estimates, more than 186,000 American men will
be
diagnosed with prostate cancer in 2008, and nearly 30,000 will die of
the
disease. Most men
should begin annual
screening for prostate cancer at age 50, which includes digital rectal
examination and the measurement of the prostate specific antigen (PSA)
level in
the blood. Men at
increased risk of
developing prostate cancer, including African-American men and all men
with a
significant family history of the disease, should begin annual
screening at age
45. Also, obesity
and a high-fat diet
have been linked to an increased risk of developing prostate cancer. Exercise, eat well, and
get screened ever
year, please.
As
for Vitamin D
supplements, the overall human clinical data, to date, has not been
very
compelling with regards to prostate cancer prevention.
However, there are a handful of ongoing
clinical research trials looking at the effects, if any, of Vitamin D
supplementation on prostate cancer risk.
Unfortunately, it may be 5 to 10 years before any
substantial results
are available from such studies.
RADIOFREQUENCY
ABLATION (RFA) OF KIDNEY (RENAL)
CANCER
Approximately
50,000 new cases of kidney (renal) cancer will be diagnosed in 2008,
and more
than 13,000 people will die of the disease, according to American
Cancer
Society estimates. Not
too many years
ago, even patients with very small tumors isolated within the kidney
faced
removal of the entire kidney. With
only one
remaining kidney, many patients faced the prospect of declining kidney
function
later in life as a complication of diabetes, untreated hypertension,
and other
disease that affect kidney function.
In
recent years, patients with small, localized kidney cancers have,
increasingly,
been able to undergo partial removal of the affected kidney, based upon
clinical research data showing no significant differences in terms of
survival
or cancer recurrence with either treatment option.
As is the case with complete removal of the
kidney (total nephrectomy), however, even partial removal of the kidney
requires a major surgical operation.
Increasingly, partial or total removal of the kidney can
be achieved
using modern minimally-invasive procedures that reduce the amount of
postoperative discomfort and recovery time.
However, these minimally-invasive approaches still carry
similar risks
of complications when compared to traditional open surgical approaches.
A
relatively
recent innovation in the minimally-invasive treatment of tumors within
solid
organs (including the kidneys) has generated a lot of interest in the
clinical
world. Radiofrequency
ablation (RFA) is
a technique whereby tumors in the kidney, liver and lung can be
treated, or
“ablated,” by inserting long needles into the tumors and heating them
with
radiofrequency current (I employ this same technique to destroy
otherwise
unresectable tumors of the liver).
In
many cases, RFA of the kidney can be performed under sedation in the
Radiologist’s office, while using a CT scanner or ultrasound machine to
guide
the ablation needle into the target tumor.
One
glaring
limitation of RFA is that, unlike the surgical removal of a tumor, one
cannot
reliably assess the adequacy of RFA treatment under a Pathologist’s
microscope,
as none of the tumor or surrounding tissues are removed from the
patient. This has
led to some concern about the use of
RFA as primary, definitive treatment for solid organ tumors, except in
those
cases where such tumors cannot be completely or safely removed by a
surgeon. Although
an array of sophisticated scanners
can be used to observe solid organs previously treated with RFA, none
of these
scans can detect microscopic residual traces of cancer cells that may
lead, in
time, to cancer recurrence and spread.
A
new research
study, just published in the journal Urology,
looked at the impact of RFA on small kidney cancers at least one year
following
RFA treatment. In
this small clinical
study, 19 patients who had previously undergone RFA of their small
kidney
cancers, at least 1 year previously (average follow-up after RFA
treatment was,
in fact, about 29 months), and who had no evidence of recurrence on
subsequent
CT scans, underwent needle biopsies of the RFA ablation site to assess
for
residual or recurrent cancer.
In
this small
study of patients with no clinical evidence of recurrence, at least by
serial
CT scans, of their kidney cancers, all kidney needle biopsies revealed
only
dead, nonviable scar tissue.
While the results of this very small
study are
tantalizing, some caution in interpreting its results is in order. The most common type of
kidney cancer (renal
cell carcinoma) is somewhat unusual, compared to most other cancers, in
that cancer
recurrence can begin to show up in the body many years after initial
diagnosis
and treatment (and after apparent cure).
And so, even with an average follow-up of just over 2
years in this
study, it is difficult to say what the long-term success rate of RFA
will look
like in these patients.
Another
caveat to
the otherwise good news contained in this study is the issue of
sampling
error. Because only
a very small sample
of tissue is recovered during needle biopsies, “false negative” results
can
arise because an area of viable tumor cells might be missed by the
biopsy
needle.
These
concerns
aside, the results of this study at least suggest that highly selected
patients
with small kidney cancers that are anatomically suitable for RFA
ablation might
be able to avoid surgery if their post-RFA CT scans show no evidence of
residual or recurrent cancer. Unfortunately,
this very small retrospective study of highly selected patients cannot
definitively tell us if RFA is an equivalent treatment to the current
surgical
methods used to manage this cancer.
Fortunately,
there are at least 3 ongoing or recently completed clinical trials
comparing
RFA with partial nephrectomy in patients with early stage kidney cancer. If the long-term results
of these studies are
favorable, then the treatment of small, early kidney cancers might
undergo yet
another revolution in terms of further minimizing the invasiveness of
treatment.
ANTISENSE
TELOMERASE
& CANCER
Without
getting
too bogged down into the arcane disciplines of molecular biology and
genetics,
telomerase, a protein manufactured in all healthy cells, restores the
frayed
ends of our chromosomes that arise each time a cell (and its complement
of 46
chromosomes) divides. Unfortunately,
most of the mature cells of our body do not produce significant
quantities of
this enzyme. Furthermore,
as our cells
age (and thus as we age), the DNA repair systems present in each of our
approximately 60 billion cells becomes increasingly less accurate and
less effective,
and the cumulative fraying of the ends of our chromosomes eventually
leads to a
phenomenon known as the Hayflick limit.
Basically, the Hayflick limit is reached when the ends of
chromosomes
become so frayed that cells can no longer divide, and the cell is then
shunted
into a cell death mode. Such
cells in
our bodies are then said to undergo senescence, and many of the effects
of
advancing age are the direct result of this phenomenon.
While
significant
telomerase levels are not seen in most mature cells of the body,
increased
activity of this enzyme has been observed in more than 90% of cancers
that have
been studied, and the presence of this protein in cancer cells is
thought to be
an important underlying reason for their acquired immortality.
A
newly published
study in the European Journal of Cancer
Prevention reports on a fascinating new approach to cancer
therapy. In this
study, Chinese researchers designed
an “antisense” telomerase gene which was, essentially, a mirror image
of the
normal telomerase gene. When
this antisense
gene is copied into the RNA template used to code for the creation of
proteins
(all enzymes are proteins, by the way), instead of actually coding for
the
telomerase protein, the antisense telomerase RNA molecule tightly binds
with
the normal telomerase RNA, thus reducing the production of this
“immortalizing”
protein in cells where the antisense telomerase gene has been inserted.
In
this
particular study, the researchers inserted the antisense telomerase
gene into
stomach cancer cells, and they then observed a dramatic reduction in
the rate
of cell growth and division in the treated cancer cells due to reduced
levels
of the telomerase enzyme. When
these stomach
tumor cells were implanted into immune-deficient mice, the untreated
cells
rapidly grew and developed into cancerous tumors.
However, when the cancers cells treated with
the antisense telomerase gene were implanted into mice, there was no
apparent
development of tumors.
This
study is
highly intriguing in that it reveals that a “molecularly targeted”
approach to
reducing cancer cell growth and division can, at least in mice,
remarkably
inhibit the growth of such cells into disease-causing tumors. Since most of the mature
cells in our bodies
do not manufacture significant levels of telomerase, while most cancer
cells
do, telomerase inhibition may hold some promise of being able to
convert cancer
cells’ malignant behavior into something more resembling normal, benign
cells. Whether or
not this same approach
will work in humans is not yet clear.
Additionally, there have been serious setbacks, and
complications,
recently in several human gene therapy research trials.
However, the results of this innovative laboratory
study raise the hope that, one day, most cancers will either be
completely curable
by molecularly-targeted therapies or, at least, be converted into
stable,
non-progressive diseases that can be controlled indefinitely with these
types
of emerging therapies.
Disclaimer:
As always, my advice to readers is to seek the advice of your physician
before making any significant changes in
medications, diet, or level of physical activity.
