National Cancer Institute 2009 Cancer Report

What Is Cancer?
Cancer is a group of diseases characterized by uncontrolled
growth and spread of abnormal cells. If the spread
is not controlled, it can result in death. Cancer is caused
by both external factors (tobacco, infectious organisms,
chemicals, and radiation) and internal factors (inherited
mutations, hormones, immune conditions, and mutations
that occur from metabolism). These causal factors may
act together or in sequence to initiate or promote carcinogenesis.
Ten or more years often pass between exposure to
external factors and detectable cancer. Cancer is treated
with surgery, radiation, chemotherapy, hormone therapy,
biological therapy, and targeted therapy.
Can Cancer Be Prevented?
All cancers caused by cigarette smoking and heavy use
of alcohol could be prevented completely. The American
Cancer Society estimates that in 2009 about 169,000
cancer deaths are expected to be caused by tobacco use.
Scientific evidence suggests that about one-third of the
562,340 cancer deaths expected to occur in 2009 will be
related to overweight or obesity, physical inactivity, and
poor nutrition and thus could also be prevented. Certain
cancers are related to infectious agents, such as hepatitis
B virus (HBV), human papillomavirus (HPV), human
immunodeficiency virus (HIV), Helicobacter pylori (H.
pylori), and others, and could be prevented through behavioral
changes, vaccines, or antibiotics. In addition, many
of the more than 1 million skin cancers that are expected
to be diagnosed in 2009 could be prevented by protection
from the sun’s rays and avoiding indoor tanning.
Regular screening examinations by a health care professional
can result in the detection and removal of
precancerous growths, as well as the diagnosis of cancers
at an early stage, when they are most treatable. Cancers
that can be prevented by removal of precancerous tissue
include cancers of the cervix, colon, and rectum. Cancers
that can be diagnosed early through screening include
cancers of the breast, colon, rectum, cervix, prostate, oral
cavity, and skin. For cancers of the breast, colon, rectum,
and cervix, early detection has been proven to reduce
mortality. A heightened awareness of breast changes
or skin changes may also result in detection of these
tumors at earlier stages. Cancers that can be prevented
or detected earlier by screening account for at least half
of all new

Consider AS for Low Grade Prostate Cancer

Physicians Urged to Consider Active Surveillance in Prostate Cancer

The most explicit call to date for expanding the use of active surveillance in the treatment of prostate cancer was made last week by the National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of leading cancer centers. Updated guidelines from an NCCN panel urge clinicians to offer active surveillance to their patients whose prostate cancers are at low risk of progressing to life-threatening disease.

Active surveillance—in the past also called “watchful waiting” and “expectant management”—refers to a strategy of forgoing immediate treatment after a diagnosis of prostate cancer in favor of regularly scheduled testing and clinical exams to closely monitor the disease. Active surveillance can include prostate-specific antigen (PSA) testing, digital rectal exams (DRE), and prostate biopsies. If, at some point, there are indications that the disease is progressing—such as significant growth in the tumor or a rapid increase in PSA level or higher tumor grade on biopsy—definitive treatments such as surgery or radiation therapy can be pursued.

Of the more than 192,000 estimated prostate cancer cases diagnosed in 2009, about half may fall in the low-risk category, explained Dr. Bhupinder Mann from NCI’s Division of Cancer Treatment and Diagnosis.

How the NCCN Guidelines Define Low Risk
Low risk
Expected survival:

Less than 10 years
Indications:

Tumor stage: T1-T2a
Tumor grade: Gleason score 2-6
PSA level: < 10 ng/mL
Patients should get:

PSA as often as every 6 months
DRE as often as every 12 months

Very low risk
Expected survival:

Up to 20 years
Indications:

Tumor stage: T1-T2a
Tumor grade: Gleason score ≤6
PSA level < 10 ng/mL
< 3 positive biopsy cores, ≤ 50% cancer in each core
Patients should get:

PSA as often as every 6 months
DRE as often as every 12 months

Under the updated guidelines (available online with free registration), active surveillance should be recommended to men with low-risk prostate cancer who have a life expectancy of less than 10 years. Men with low-risk cancers have a relatively low PSA level and their tumors are small, confined to one side of the prostate, and have a low tumor grade, or Gleason score (see sidebar). The guidelines also established a new category of very-low risk, or clinically insignificant prostate cancer. In men with a life expectancy of up to 20 years who fall into this new category, the guidelines recommend advising only active surveillance as the preferred management approach.

“The entire [prostate cancer] treatment committee is concerned about the overdiagnosis and overtreatment of prostate cancer,” explained the panel’s chair Dr. James L. Mohler from the Roswell Park Cancer Institute. The impetus for the update, Dr. Mohler continued, was the publication last year of results from two large clinical trials of prostate cancer screening that showed there was significant overdiagnosis and overtreatment of cancers that likely would have never been a cause for concern.

“Most men find out that they have prostate cancer and what do they want? They want it gone,” Dr. Mohler said. “There are too many men suffering the side effects of treatment, and society is bearing the costs of those treatments. And too much of it is unnecessary.”

To that point, a study published last September estimated that, since 1986, as many as 1 million men have received definitive treatment for a prostate cancer (diagnosed as a result of PSA screening) that would have never threatened their lives. Despite the concerns about overtreatment and the call to expand active surveillance, Dr. Mohler stressed that it’s still an individual decision that patients must make in consultation with their physicians.

Although there are clear benefits to active surveillance in the appropriate patients, the guidelines panel noted that choosing this treatment approach is not a simple process or decision. In addition to the need for frequent exams and tests, from a disease perspective, waiting to see if the cancer progresses could eventually mean having to treat a more aggressive tumor, with a lower likelihood of cure and a greater risk of serious side effects.

The risk of such progression, Drs. Mann and Mohler agreed, is low. According to Dr. Mohler, the risk of a significant tumor grade increase is around 5 percent, and the risk of an increase in PSA is between 16 and 25 percent.

No data have been published from randomized clinical trials directly comparing active surveillance to immediate, definitive treatment. But based on the available evidence, Dr. Mann said, “In low-risk patients, active surveillance with delayed curative intervention is an acceptable strategy.” That contention is supported by two recently published studies (here and here) which both reported equivalent long-term cancer mortality outcomes in men who opted for active surveillance compared with those who received immediate, definitive treatment. (See the cancer research highlight in this issue on a comparative effectiveness study released last week.)

Dr. Paul Godley, a medical oncologist at the University of North Carolina Lineberger Comprehensive Cancer Center, said the recommendations are overdue. However, he noted, there are still questions about active surveillance that need to be worked out, including the appropriate trigger for transitioning to definitive treatment. “I think that will still be fairly subjective based on what the patient and his physician are comfortable with,” he said.

There’s also the matter of how clinicians will react to the updated recommendations, given that immediate, definitive treatment appears to be a fairly ingrained practice. An online poll conducted January 2009 via the New England Journal of Medicine, for instance, presented a case example of a 63-year-old man with low-risk prostate cancer. Among the respondents from the United States (not all of whom were clinicians), approximately 70 percent chose either radiation therapy or surgery over active surveillance as the preferred management option.

It is unclear, Dr. Godley said, whether the recommendation “will make the trend lines change a whole lot.” But, he continued, “it may make some physicians more comfortable with doing active surveillance themselves or referring patients to a group that is using it in their low-risk patients.”

—Carmen

Why We need a PSA Test

Cancer PSA Test TODAY
OurGoodHealth.com | 01.19.2010
Prostate cancer kills if allowed to grow. If ever there was a good reason to have a simple blood test, this is it. The prostate cancer PSA (prostate specific antigen) test is one of the tests given to determine if cancer cells are present in an otherwise healthy prostate. It is a simple blood test to help doctors diagnose and identify the existence of prostate cancer.

The PSA test, although considered a prostate-specific test, is not really an absolute definitive test for the cancer. Depending on the research conducted, the PSA test is known to be somewhere between 85 and 95% accurate in identifying prostate cancer.

While an elevated PSA test may suggest the presence of prostate cancer, it’s not an absolute. If however you have an elevated result, your doctor will probably want to do additional testing for a more complete and accurate assessment of the potential cancer. The last thing you want to do is to allow prostate cancer to grow beyond the prostate gland.

The good news is that BPH or benign prostatic hyperplasia, better known as an enlarged prostate, can also elevate the PSA test results. Even prostatitis and lower urinary tract symptoms can show elevated levels of PSA so if you have an elevated test result, don’t panic! A normal result from a PSA test doesn’t guarantee that you're free from cancer, nor does a higher-than-normal result mean you do have cancer.

It’s critical that you follow your doctor’s lead in regard to dealing with the prostate specific antigen test results. The results are an indication, as a tool only to develop a complete diagnosis. To complicate matters more, PSA levels can also increase with age. Oh, and the relative size of your prostate also plays a factor in interpreting the results.

Remember that as many as two out of three people with elevated PSA readings DO NOT have a malignancy.

Here’s a quick list of the benefits and reasons why you should consider getting a PSA test:

1. It’s possible to detect a cancerous condition before any symptoms are known.

2. Early detection catches prostate cancer before it has spread, increasing the chances of a complete cure.

3. The PSA blood test has been recognized as a contributing factor that has significantly reduced the number of prostate cancer deaths.

The PSA test also can deliver a false positive, about 20% of the time. Still, the test is recognized as a good indicator of potential cancerous conditions and should be taken seriously.

A 2005 Harvard study indicated that men having an annual PSA test were almost three times LESS likely to die of prostate cancer than men who didn’t bother with the test. So, the best reason to have the test is that without it, you greatly increase the chances of dying from prostate cancer!

Copyright OurGoodHealth.com 2010

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Appropriate Frequency of Spinal MRI Scans in Men With Metastatic CRPC
ProstateCancerInfoLink.net | 01.16.2010

Similar Effectiveness of PCa Treatment Options

Report suggests similar effectiveness among options for managing low-risk prostate cancer

Institute for Clinical and Economic Review summary incorporates findings from 3 separate appraisals of 6 treatment options

A comprehensive appraisal of the management and treatment options for low-risk prostate cancer found that the rates of survival and tumor recurrence are similar among the most common treatment approaches, although costs can vary considerably. The report was prepared by the Institute for Clinical and Economic Review (ICER), a leader in comparative effectiveness research based at the Massachusetts General Hospital's Institute for Technology Assessment.

Bringing together the findings from three previous reviews completed by ICER, the final summary report, "Management Options for Low-Risk Prostate Cancer: A Report on Comparative Effectiveness and Value," compares multiple approaches to managing the most common non-skin cancer among U.S. men:

• Active surveillance, a "watch and wait" strategy with careful monitoring and referral for surgery or radiation if necessary;
• Radical prostatectomy, surgical removal of the prostate via traditional "open" or robot-assisted approaches;
• Brachytherapy, implantation of radioactive seeds in the prostate;
• Intensity-modulated radiation therapy (IMRT) and proton therapy, two forms of external radiation therapy.

The ICER review found that there are no definitive head-to-head studies comparing these options, but that accumulated evidence from multiple studies over the years suggests that overall survival and the rate of cancer recurrence are quite similar among all options, including active surveillance. There are different risks for certain side effects and complications, but no treatment option stands out as superior overall. Because low-risk prostate cancer is typically slow-growing and may not cause any symptoms, active surveillance is a reasonable option, particularly for men 65 and older, approximately half of whom will never have their cancer progress to the point of requiring treatment.

"ICER's review provides a welcome objective summary of what we know and what we don't know that can help men in conversations with their doctor," stated David Most, PhD, prostate cancer survivor and Founder and President of Health Information Research, Inc., who was a member of the Evidence Review Group that participated in the ICER appraisal process. "Given the numerous sources of information we have on the different management options, it really can be difficult to know what to do. Having a report like this from ICER will help patients make informed healthcare decisions that reflect their values about the risks and benefits among the different options."

The ICER report included a review of published literature on the treatment of low-risk prostate cancer as well as simulation modeling to project the long-term effects of each treatment approach. The evidence on radical prostatectomy, brachytherapy, and IMRT was judged to demonstrate comparable overall clinical effectiveness for most men, while there was not enough evidence to date to make a comparison on proton therapy. The evidence on active surveillance was stronger for older men, and therefore ICER rated its clinical effectiveness as comparable to immediate treatment for men 65 and over. Long-term outcomes with active surveillance are not yet available, but for younger men active surveillance may still be a reasonable option given that surgery or radiation can be done if regular blood tests and prostate biopsies suggest the cancer is growing. The ICER report also found that, based on Medicare payments, active surveillance costs approximately $300-$1,000 per year, while brachytherapy and radical prostatectomy procedures cost approximately $10,000. IMRT and proton therapy are more expensive, costing $20,000 and $35,000 per treatment course, respectively.

"ICER works hard to create unbiased, fully-informed appraisals of disease management and treatment options so that patients, clinicians, and payers can trust the information produced," stated Steven D. Pearson, MD, MSc, FRCP, President of ICER. "The results of the summary report on low-risk prostate cancer are an example of how scientifically-sound comparative effectiveness research can be presented in an actionable way for multiple audiences. Ultimately, this type of research can help improve patient outcomes and overall value in the healthcare system. "

Stored Fats Fuel Aggressive Cancer Growth

Cancer Cells Use Stored Fats to Fuel Aggressive Growth and Spread

An enzyme that is best known for breaking down stored fats in cells may be co-opted by cancer cells so that they can become more aggressive, Scripps Research Institute investigators have reported. Blocking the activity of the enzyme, MAGL, in cell lines of several aggressive cancers and in mouse models derived from the cell lines significantly tempered cell migration and tumor growth, Dr. Daniel Nomura and colleagues reported January 8 in Cell.

In the same mice in which MAGL levels were reduced, the research team found that a high-fat diet could kick start tumor growth. This latter finding, they wrote, “has provocative implications for the crosstalk between obesity and tumorigenesis.”

To conduct the study, the researchers first analyzed the expression of certain types of enzymes in cell lines of aggressive and non-aggressive melanoma, breast, and ovarian cancer. They found that MAGL levels were significantly elevated in the aggressive cell lines. They also found that when they increased MAGL levels in the non-aggressive cancer cell lines, the cancer cells became more aggressive.

MAGL promotes this aggressive posture in cancer cells, the researchers discovered, by unleashing free fatty acids (FFAs), which are integral components of cell membranes and other molecules in cells. The increased production of FFAs, in turn, stimulates the activity of a communication network of signaling lipids known to enhance the growth of tumors and movement of cancer cells. In the mice with inhibited MAGL expression fed a high-fat diet that led to increased tumor growth, the researchers noted, the tumors had significantly elevated levels of FFAs.

The study’s findings provoke “many exciting new questions,” wrote Drs. Jessica Yecies and Brendan Manning from the Harvard School of Public Health in an accompanying editorial. Among them is whether MAGL levels could “be used as a biomarker to predict the influence of dietary fats and obesity on tumor progression