THIS IS GOOD NEWS!!!!! -- Dr. Dale



Dramatic Decline in CRC in US Attributed to Colonoscopy

The latest statistics on colorectal cancer (CRC) in the United States, which go up to 2010, show that both incidence and mortality rates continue to fall.

Overall, deaths from CRC have been falling at around 3% per year over the last decade (2001 to 2010). Overall incidence rates have also been falling, by an average of 3.4% per year, but there is a marked variation by age. Incidence is decreasing in adults over 50 years of age, with a particularly sharp drop in the over-65s, attributed to colonoscopy, but it has increased slightly in younger adults under the age of 50. And blacks still have the highest burden of disease; they are 25% more likely to be diagnosed with colorectal cancer and 50% more likely to die from the disease than whites.

The findings, by Rebecca Siegel, MPH, and colleagues from the American Cancer Society, were published online March 17 in CA: A Cancer Journal for Clinicians.

The team analyzed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program and the Centers for Disease Control and Prevention's National Program of Cancer Registries, as provided by the North American Association of Central Cancer Registries (NAACCR).

Dramatic Decline in the Over-65s

The researchers highlight the "dramatic decline" in CRC incidence seen in older adults (over 65s); it was falling at a rate of 3.6% from 2001 to 2008, but this decline accelerated in the last 2 years for which data are available, to 7.2% from 2008 to 2010.

This fall is probably related to the higher screening rates in this age group, Siegel told Medscape Medical News. Adults 65 and older have fewer barriers to screening related to cost because they are eligible for Medicare, which has covered colorectal cancer screening even for those at average disease risk since 2001.

In 2010, 64% of adults 65 and older reported being current for colorectal cancer screening versus 55% of adults 50 to 64, she noted. Although there are several different tests available for CRC screening, the "dramatic declines in incidence in recent years have been largely attributed to the uptick in colonoscopy because it is the only test for which use increased from 2000 to 2010; use of fecal immunochemical testing and sigmoidoscopy declined during that time period," she explained.

Colonoscopy offers a double whammy in that it can both prevent CRC by detecting and removing precancerous polyps and detect the cancer in its early stages, when there is a better chance of successful treatment.

Stool tests are very good for detecting cancer early, but much less able to lower incidence by detecting precancerous lesions, Siegel told Medscape Medical News.

Used to Be Top Cancer Killer

Back in the late 1940 and early 1950s, CRC was the most common cause of cancer death, the researchers note.

Now it has dropped to the third leading cause of cancer death (after lung cancer and prostate cancer in men and breast cancer in women).

This is in part due to historic changes in risk factors (such as decreased smoking, decreased red meat consumption, and increased use of aspirin), as well as the introduction and dissemination of early detection tests and improvements in treatment, the researchers write.

"This is great news," Siegel commented. "Colorectal cancer is 1 of only 2 cancers that we can actually prevent through screening, with cervical cancer being the other."

"Unfortunately, many adults — 23 million Americans — who should be screened for colorectal cancer have never been tested. It's important to get the word out about how life-saving these screening tests are," she said.

This point was highlighted in a press release from the American Cancer Society (ACS). The continuing drops in CRC incidence and mortality "show the lifesaving potential of colon cancer screening," commented Richard Wender, MD, chief cancer control officer at the organization.

The data in the study show that colonoscopy screening (in adults aged 50 to 75 years) increased from 19% in 2000 to 55% in 2010.

Dr. Wender highlighted an initiative from the National Colorectal Cancer Roundtable that aims to increase screening rates to 80% by 2018.

Disturbing Increase in Younger Adults

While the overall incidence of CRC has been falling over the last decade, the researchers note a distinct age divide — with a decrease of 3.9% per year among adults aged over 50 years, but an increase in incidence of 1.1% per year among adults under 50 years of age.

This increase in CRC among younger adults was confined to tumors of the distal colon (increasing by 1.3% per year) and the rectum (1.8% annually).

"Although the cause of this increase is unknown, the rise in obesity prevalence and the emergence of unfavorable dietary patterns have been implicated," they write.

A similar trend has been reported in Norway, the researchers note.

"We were actually among the first to publish this disturbing trend in 2009," Siegel commented. "Although the obesity epidemic is the obvious culprit, the rise is the strongest for rectal cancer and a link between obesity and rectal cancer has not been firmly established in women."

"It's important to note that ACS guidelines do recommend colorectal cancer screening beginning at age 40 for adults with first-degree relatives who were diagnosed with 1 or more polyps before age 60," she said.


[Follow up is important] even in young adults who are unlikely candidates for the disease.


"It is also important that clinicians are diligent about follow-up of colorectal cancer symptoms, even in young adults who are unlikely candidates for the disease," she added.

Higher Burden in Blacks

The review shows blacks continue to have the highest burden of disease.

The incidence of CRC is highest in blacks (approximately 25% higher than in whites), and there is an even greater disparity for CRC mortality rates, which are approximately 50% higher in blacks compared with whites (29.4 vs 19.2 per 100,000 population).

"A higher prevalence of risk factors and lower screening prevalence contributes to both the higher incidence and mortality in blacks," Siegel commented.

"In addition, blacks have lower survival than whites even for similar-stage disease. This is because blacks are less likely to receive standard-of-care treatment, including surgery, adjuvant chemotherapy, and radiation," she explained. Studies show that for similar-stage disease, equal treatment results in equal outcomes, she added.

In the study, the researchers trace back the history of this disparity. CRC mortality used to be lower in blacks compared with whites in the 1960s, and the racial crossover occurred around 1970 for women and 1980 for men. After that, rates diverged rapidly over the next 3 decades. During the 1980s and 1990s, steep declines had begun in whites, but the rates in blacks were still increasing (in men) or were stable (in women). This mortality gap appears to have leveled off in recent years, the researchers write. From 2006 to 2010, annual declines in mortality rates were similar among black and white men, and slightly larger among black than white women.

"The good news is that the gap in mortality rates between blacks and whites appears to have peaked in the mid-2000s and may be slowly growing smaller," Siegel commented.

A less scary colonoscopy?!

This is great research!!  Just had to share. -- Dr. Dale


Novel Stool DNA Test May Enhance Colon Cancer Screening

March 19, 2014

An investigational multi-target stool DNA test for screening colorectal cancer detects significantly more cancers than the currently available fecal immunochemical test (FIT), researchers report.

But it does so at the cost of more false-positive results.

"This new test is the most sensitive noninvasive test for detecting colorectal cancer," said lead study author Thomas F. Imperiale, professor of medicine at the Indiana University School of Medicine in Indianapolis.

"The advantages are that it could be done less frequently than annually. We are going to have to have computer simulation analyses tell us what an appropriate interval would be," he told Medscape Medical News in a telephone interview.

"The new test is very good at detecting curable-stage cancers. If there is a downside, it's that the specificity is not as good as FIT. That's the way it goes with diagnostic tests. The more sensitive they are, usually the less specific they are," he said.

The study was published online March 19 in the New England Journal of Medicine.

The test, known as Cologuard, is produced by Exact Sciences and was codeveloped by the Mayo Clinic. It consists of quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. The test is currently under review at the US Food and Drug Administration; the company is scheduled to appear before the Molecular and Clinical Genetics Panel of the Medical Advisory Committee on March 27.

Noninvasive Alternative to Colonoscopy

Despite widespread recommendations and the availability of several screening tests, a substantial proportion of the American population does not get screened. The noninvasive nature of this stool DNA test might make colorectal cancer screening more acceptable, Dr. Imperiale said.

He and his team evaluated 9989 asymptomatic people 50 to 84 years of age who were considered to be at average risk for colorectal cancer and who were scheduled to undergo a screening colonoscopy.

All participants provided a stool specimen before routine bowel preparation for colonoscopy.

On colonoscopy, colorectal cancer was identified in 65 participants — a prevalence of 0.7%. Of these, 60 had stage I to III cancers. In addition, advanced precancerous lesions were identified in 757 (7.6%) participants.

Stool DNA testing identified 60 of the 65 participants with cancer, for a sensitivity of 92.3%, including 56 of the 60 participants with stage I to III cancers, for a sensitivity of 93.3%.

DNA testing sensitivity did not vary significantly by cancer stage or location in the colon, Dr. Imperiale reported.

DNA testing also identified 321 of the 757 advanced precancerous lesions, 27 of the 39 (69.2%) participants with high-grade dysplasia, and 42 of the 99 (42.4%) participants with sessile serrated polyps 1 cm or larger.

The sensitivity of the DNA test increased as lesion size increased, and was higher for distal advanced precancerous lesions than for proximal lesions (54.5% vs 33.2%).

Age did not affect its sensitivity for detecting cancer.

For the 9167 participants who had colonoscopy findings other than colorectal cancer or advanced precancerous lesions, such as nonadvanced adenomas or negative results, the specificity of the DNA test was 86.6%.

For the 4457 participants with negative colonoscopy results, the specificity of the DNA test was 89.8%. In this subgroup, specificity was 94.0% for participants younger than 65 years and 87.1% for those 65 years and older.

For colorectal cancer, overall sensitivity was significantly better with DNA testing than with FIT (92.3% vs 73.8%; P = .002).

The sensitivity of DNA testing was also better than of FIT for advanced precancerous lesions (42.4% vs 23.8%; P < .001).

However, for people with nonadvanced or negative findings on colonoscopy, specificity was worse with DNA testing than with FIT (86.6% vs 96.4%; P < .001).

To detect 1 cancer, 154 people would need to be screened with colonoscopy, 166 with DNA testing, and 208 with FIT.

Number of False-Positives With Stool DNA Concerning

Results with this stool DNA test are "encouraging", said Douglas Robertson, MD, chief of gastroenterology at the White River Junction Veterans Affairs (VA) Medical Center in Vermont and associate professor of medicine at the Dartmouth Medical School in Hanover, New Hampshire.

He and his colleague, Jason A. Dominitz, MD, from the VA Puget Sound Health Care System and the University of Seattle, coauthored an accompanying editorial.

"The test is showing progress in terms of being able to detect cancer, but it remains to be seen how it will function in real-world clinical practice," Dr. Robertson told Medscape Medical News.


Dr. Douglas Robertson

"Ultimately, one of the dictums of colorectal cancer screening is that the best test is the one that gets done," he noted.

Another concern is the false-positive rate. The more frequently the test returns a false-positive result, the more colonoscopy exams will be required, he explained.

The interval with which this test would be applied in clinical practice is also not clear, Dr. Robertson said. "It probably can't be applied every year because the false-positive rate would be pretty high and you might end up doing colonoscopies on everybody over time anyway," he said.

"These are real-world practical issues that still need to be sorted out with stool DNA testing," he said. "It's exciting because the test clearly is functioning better than FIT, but how it will translate into clinical outcomes in practice we don't yet know."

Dr. Robertson said the results of this study could help to inform the US Preventive Services Task Force (USPSTF) as it re-evaluates recommendations for colorectal cancer screening.

"Right now, the USPSTF recommends 3 tests: colonoscopy, sigmoidoscopy, and stool testing with FIT. The last time they looked at the data, they didn't think there was enough support for fecal DNA testing so they did not endorse or recommend its use. This study might change that. Before, fecal DNA technology picked up about 50% of the cancers; now, in a similar study years later and with a newer version of the test, fecal DNA is detecting more than 90% of cancers," he explained.

"It is definitely working better than it used to; there's no question about that, Dr. Robertson said. "Whether the USPSTF will recommend it as an option remains to be seen."

The study was supported by Exact Sciences Inc. Dr. Imperiale has disclosed no relevant financial relationships. Dr. Robertson reports being on the advisory board of Pill Cam Colon (Given Imaging).