In recognition of Colorectal Cancer Awareness Month, the American College of Obstetricians and Gynecologists are urging their members to remind their patients over age 50 to be screened for colon and rectal cancer.

Frequently, obstetricians-gynecologists are the only doctors that women see regularly.  As such, they can help increase colorectal screening rates and prevent colorectal cancer.

Colorectal cancer is an equal opportunity killer, affecting both men and women equally. In 2007, nearly 75,000 women will be diagnosed with colorectal cancer and more than 26,000 will die from it.

Douglas W. Laube, MD, MEd, president of the American College of Obstetricians and Gynecologists points out,

Despite the promising decline in colorectal cancer deaths in the US, many women are still not getting screened for colorectal cancer.  Ob-gyns can really help by making sure that all eligible patients leave their office with screening recommendations. ACOG encourages its members to educate women about the importance of routine colorectal cancer screening.

After reviewing existing evidence for use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS) to prevent colorectal cancer, the US Preventive Services Task Force (USPSTF) has concluded that its harms outweigh its benefits.

The USPSTF assessment:

Overall, the USPSTF concluded that harms outweigh the benefits of aspirin and NSAID use for the prevention of colorectal cancer.

The recommendation applies to adults at average risk of colorectal cancer without symptoms, including those with a family history of colon or rectal cancer.  It does not include people with familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (Lynch I or II), or a history of colorectal cancer or adenomatous polyps.

The Task Force did say that doctors should continue to discuss the use of low-dose aspirin to prevent coronary heart disease because there is evidence that aspirin does reduce deaths from heart disease.

Colorectal cancer is the third most common cancer for both men and women and the second leading cause of cancer death.  Most colorectal cancer begins with adenomas (polyps) in average risk people over the age of 50.

The USPSTF is an independent panel of experts in primary care and prevention that systematically reviews evidence and effectiveness for clinical preventive services and develops recommendations for the use of those interventions.

USPSTF found the following evidence of benefits of aspirin or NSAID use:

• Fair to good evidence that aspirin and NSAIDS taken in higher doses over longer periods of time reduce the incidence of adenomatous polyps.
• Good evidence that low-dose aspirin does not reduce incidence of colorectal cancer.
• Fair evidence that aspirin in higher doses than those used to prevent coronary artery disease and NSAIDS may be associated with a reduction in the incidence of colorectal cancer.
• Fair evidence that aspirin used over longer periods of time may be associated with lower incidence of colorectal cancer.
• Poor evidence that aspirin and NSAID use reduces death from colorectal cancer.

The panel also found evidence of harms of aspirin and NSAID use:

• Good evidence that aspirin increases the risk of gastrointestinal bleeding related to dosage.
• Fair evidence that aspirin increases the risk of a hemorrhagic stroke.
• Good evidence that NSAIDS increase the risk of gastrointestinal bleeding and kidney problems, particularly in the elderly.
• Good evidence that one type of NSAIDS — COX-2 inhibitors — increase the incidence of kidney problems.
• COX-2 inhibitors appear to be associated with increased risk for cardiovascular events.
• Overall there is good evidence for at least moderate harms associated with aspirin and NSAIDS.

More than 80 percent of colorectal cancers will arise from adenomas, which are very common in people over the age of 50.  Thirty to fifty percent of adults over 50 will develop adenomas, but few of those polyps will progress to colorectal cancer.  Risk of polyps and of colorectal cancer increases as people get older.

The Task Force emphasizes the importance of screening for colorectal cancer, regardless of aspirin or NSAID use.   The USPSTF strongly recommends screening for all men and women over 50 for colorectal cancer.

SOURCE:  Annals of Internal Medicine, March 6 2007, Volume 146,Issue 5, Pages 361-364.

WHAT THIS MEANS FOR PATIENTS AND THE COMMUNITY

Routine use of aspirin and NSAIDS is more harmful than beneficial in preventing colorectal cancer.  It takes a higher dose of aspirin over a longer period of time to prevent the type of polyps that have the potential of turning into cancer.  Doses high enough to prevent adenomatous polyps also carry a risk of gastrointestinal bleeding, stroke, and kidney problems.  The elderly are especially at risk.

COX-2 inhibitors, such as Vioxx® and Celebrex®, increase the risk of kidney problems and appear to be associated with cardiovascular events.

The recommendations against routine aspirin or NSAID use do not apply to people with genetic conditions including FAP and hereditary non-polyposis colorectal cancer or to people with a history of polyps or colorectal cancer.  These individuals should discuss the risk and benefits of aspirin or NSAID use with their doctors.

However, the recommendation does apply to people with a family history of colorectal cancer who do not have a known genetic mutation.

Governor of Michigan Jennifer M. Granholm has recognized March 2007 as Colorectal Cancer Awareness Month, part of a national effort to increase awareness of a serious, but preventable, disease that affects many citizens of Michigan.

Janet Olsweski, Director of the Michigan Department of Community Health said,

Colorectal cancer is one of the most preventable forms of cancer. Screening not only detects the disease at an early, curable stage, but it can also prevent it by finding and removing polyps-or precancerous growths-that might become colorectal cancer.

Although the Michigan Cancer Consortium recommends colorectal cancer screening for men and women beginning at age 50, only 53 percent of Michigan adults age 50 and older have been screened.

Colorectal cancer is the second leading cause of cancer-related death in Michigan.  According to American Cancer Society estimates 1,750 people in Michigan will die of colorectal cancer in 2007 and there will be 5,570 new cases of colon or rectal cancer diagnosed.

This morning I posted some exciting research from France that reports on a gene expression signature that predicts whether someone with colorectal cancer will respond to FOLFIRI treatment. 

Instead of having to try the chemotherapy, wait several weeks, and run scans to see if the tumor is getting smaller, testing for fourteen genes in a patient’s tumor could tell doctors right away whether it was worthwhile to treat with FOLFIRI.

When I was first diagnosed with colon cancer nearly 25 years ago, there was one drug used to treat it — 5FU or fluorouracil.  It had been around since the fifties, not very effective, but the only thing available.  When a modifier drug — either levamisole or leucovorin — was added to it, it just about doubled expected survival time.  But that still was only a year.

Today standard treatment still has the old standby 5FU as the backbone of treatment, but two new chemotherapy drugs are available along with three biologic agents and an oral form of 5FU.  Median survival has doubled again, to two years.

The problem with these new choices is making the choice.  What works best for what patient.  Will the tumors shrink?  Will patients have life-threatening side effects?  What should we start with?

Like other cancers, colon and rectal cancer has entered a brand-new era of personalized medicine.  Giving the right treatment to the right patient at the right time will save frustration and unnecessary misery.  For some patients, it will save lives.

The French research team dug through more than 14,000 genes before they narrowed down their search to 14.  This is painstaking, difficult laboratory work.  It is made possible by better technology and bigger and faster computers.  It would have been impossible twenty-five years ago.  It would have been impossible even ten years ago.

But it is not only possible today — it’s happening.  We may soon be able to decide the best treatment or whether someone needs chemotherapy at all.

This is expensive research and demands highly skilled scientists. Many experiments will lead nowhere and scientists will have to begin over and try again.  We need to have the patience to support it and the willingness to pay for it.

Cuts in research funding for the National Cancer Institute demoralize these dedicated scientists and jeopardize their work.  We have to fund the fight!

Colorectal cancer is preventable, treatable, and beatable.

Deciding what chemotherapy treatment is best for an individual patient is difficult.  Only about half of patients with colon or rectal cancer will respond to a specific drug combination and even the responders will eventually become resistant to the drug.

Chemotherapy becomes a process of trial and error, giving drugs and watching for tumors to shrink (respond), remain the same (stable disease), or get larger or more numerous (progress.)  This is a slow and tedious process during which up to half of patients are actually getting treatment that doesn’t benefit them — and missing out on a different treatment that might help.

Researchers in France have identified a signature of 14 genes that predict response to FOLFIRI — the combination of irinotecan fluorouracil, and leucovorin.  FOLFIRI is one of the standard first-line combination treatments for colorectal cancer.

Working with tumors from 21 patients with colorectal cancer that had spread to the liver but could not be surgically removed, they found that there were 14 genes that very accurately predicted who would and who would not respond to FOLFIRI treatment.  Nine patients (43%) did respond to FOLFIRI and all had the 14 gene signature.  Eleven did not respond, and 10 of the 11 did not have the profile.

There was no difference in other patient characteristics that might have predicted the difference in response. 

While the gene signature analysis was based on a small number of patients, the research team believes that it stable and reliable.  However, they are currently involved in a larger study with more patient in several different institutions to validate their findings.

Eventually, they plan on a large, randomized clinical trial that would test whether using the 14 gene signature to choose treatment with FOLFIRI would improve survival of people with metastatic colorectal cancer.

SOURCE: Del Rio et. al, Journal of Clinical Oncology, Vol 25, No 7 (March 1), 2007: pp. 773-780.

WHAT THIS MEANS FOR PATIENTS

This is an early study which needs to be validated in a larger group of patients and then tested in a randomized clinical trial.  It isn’t ready to be used to predict response to treatment yet.

It is not available to help make decisions about the right treatment for an individual patient right now.