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.

Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center:

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html

Send your feedback to Dr. Wascher at: rwascher@doctorwascher.net

http://www.doctorwascher.com

Copyright 2008. Robert A. Wascher, MD, FACS.

All rights reserved.

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