Colorectal Cancer Screening: Which Test Is Best?

It is widely accepted that the best way to determine whether screening can reduce deaths from cancer is with a randomized controlled trial (RCT), where half of a large group of people are invited to get a screening test, and scientists measure whether their risk of death is decreased compared to the half who did not receive an invitation to get screened. When it comes to colorectal cancer, we have that kind of evidence for fecal occult blood testing (FOBT, or stool testing) and for flexible sigmoidoscopy. But there has never been an RCT for colonoscopy, although several are now underway. The evidence supporting the value of colonoscopy has largely been based on inference.

A pair of new studies in this week’s New England Journal of Medicine provide new evidence supporting the value of colonoscopy in reducing colorectal cancer deaths, principally as a result of the detection and removal of precancerous polyps. We asked Robert A. Smith, PhD, senior director of cancer screening to comment on the significance of the new data.

“A persistent question related to colorectal cancer screening has been, ‘which test is best?’ The American Cancer Society colorectal cancer screening guidelines currently endorse seven different screening tests, including three stool tests, two endoscopic tests, and two radiographic tests. Each has been shown to be effective, but it is difficult to say one test is better than the other.

“The most recent ACS guidelines prioritize colorectal cancer screening tests that are more likely to identify adenomatous polyps, which are known precursors of colorectal cancer. Tests that visualize the colon, i.e., endoscopic tests and radiographic tests are more likely to detect polyps compared with stool tests.

“Two studies in this week’s New England Journal of Medicine help fill in some blanks. The first, by Zauber and colleagues at Memorial Sloan-Kettering Cancer Center, finds that removing pre-cancerous polyps during colonoscopy ultimately resulted in reduced colorectal cancer incidence, and eventually 53% fewer colorectal cancer deaths compared with the expected death rate in the general population. Yet, modeling data show that what colonoscopy achieves in one visit, high sensitivity stool tests, such as the fecal immunochemical test (FIT), have a good chance of achieving with annual testing over a ten year period.

“Actual empirical data is preferable to modeling data, and the initial results from a prospective randomized trial in Spain in the same issue of the journal holds the promise of eventually providing a prospective comparison of colonoscopy and high sensitivity stool testing. In this study, one-time colonoscopy is being compared to receiving FIT every two years in a population of 53,000 adults ages 50-69. In the first round of screening, the rate of colorectal cancer detection was higher in the colonoscopy group compared with the FIT group, and the rate of advanced adenoma detection was twice as high. This is expected since test-sensitivity is higher in colonoscopy compared with stool testing. As the study proceeds, we would expect the FIT group to ‘catch up,’ and if our models have been correct, the performance of the two tests over a 10 year period should become more similar. The success of this head-to-head study depends on making sure the study’s participants continue getting biennial FIT testing, something rarely achieved outside of a study. Longer follow-up likely will be needed in the first study, as well, to measure whether the lifesaving benefits of removing precancerous polyps will persist.

“In an editorial accompanying the studies, independent scientists suggest that colonoscopy could be used to help determine an individual person’s risk, based on the presence or absence of polyps at an initial screening at age 60. The idea of hybrid screening, where adults of different genders and different risks begin and end screening at different ages and are screened with different technologies based on risk is not a new idea, but this idea is still in its infancy, so we’re a long ways from proposing a practical alternative to the current guidelines which recommend that average risk adults begin screening at age 50 with either colonoscopy every 10 years, or annual high-sensitivity stool tests.”

Supplies of Lifesaving Childhood Cancer Drug Critically Short

Update Feb 20, 2012: The U.S. Food and Drug Administration has now taken steps to increase the supply of two cancer drugs, Doxil and methotrexate. The FDA will allow a temporary importation of the drug Lipodox, a replacement for Doxil to meet patient needs in the coming weeks. The FDA also approved a new manufacturer of methotrexate. You can read the FDA press release on the actions here, and see comments from the American Cancer Society Cancer Action Network (ACS CAN) and Dr. Len Lichtenfeld, deputy chief medical officer here.  

News in the New York Times that in a matter of weeks, hospitals across the country may run out of a  crucial medicine to treat childhood leukemia has resurfaced the issue of drug shortages.

Last September, our advocacy affiliate, the American Cancer Society Cancer Action Network (ACS CAN) came out in support of a bill that would require drug companies to give the FDA advance notification of issues that could lead to shortages, in hopes of allowing officials to prepare and respond.

In a letter to bill sponsors, Christopher W. Hansen, president of ACS CAN said:

“Advance notification to the FDA from industry about the potential suspension of drug production, an interruption in manufacturing, or other production adjustments that might lead to a shortage would put the FDA in a better position to track and manage potential drug shortages. Notification would also allow government, industry, providers and the public to more systematically analyze and understand the causes of specific drug shortages as they occur, and to develop appropriate real-time solutions that are also needed to address the ongoing acute problem that cancer patients are living with daily.”

Dr. Len Lichtenfeld, the American Cancer Society’s deputy chief medical officer and resident blogger, also testified to FDA about the drug shortage crisis and its impact on people with cancer:

“There appear to be numerous contributing factors to the shortages, and these factors may contribute differently to the shortages of particular drugs. The market system for pharmaceuticals has served patients well for many years, but we have to ask why is it failing now.

“We strongly support the efforts of the FDA and other agencies to develop a better understanding of the root causes of the current crisis. We also call on the pharmaceutical industry act expeditiously to provide the public with a full understanding of why and how this crisis has arisen.

“However, until the causes of the shortages are better understood, interim steps should be taken by the government to minimize adverse effects for patients to the maximum degree possible.

“Through administrative action, the federal government should:

• Immediately expand its collection of information on the underlying causes of the current drug shortages. Clinicians and patients need better information about shortages and better options for purchasing the drugs they need for their treatments.
• Compile available inventories of drugs that are in short supply, including where shortages exist.
• Work with interested parties as information becomes available about the causes of specific drug shortages to resolve  those shortages. For example, adequate production to meet demand in the near term could be leveraged by the National Cancer Institute’s infrastructure for drug development to provide short-term supplies for individual cancer drugs.”

As Len said at the time, every day that passes without available cancer drugs means fewer lives may be saved.

Weighing the Risks and Benefits of Breast Cancer Prevention Drugs

Do the benefits of taking a medication to prevent breast cancer outweigh the potential risks? That’s the question a new study published Monday in the journal Lancet Oncology is raising about exemestane, a cancer treatment that many scientists hope could also be used for breast cancer prevention.

Exemestane (also known by the brand name Aromasin) is currently used as an additional therapy to treat patients with breast cancer following the initial surgery to prevent the cancer from returning, and in women with advanced disease.  It has also proven effective in significantly reducing (by 65 percent) the risk of developing breast cancer in post-menopausal women at high risk for the disease.

However, the Lancet study highlights a troubling side effect: use of the drug may also cause significant loss of bone mineral density or BMD, leaving a patient at increased risk for bone fractures and osteoporosis later in life.

Researchers looked at 351 women over a period of two years, and monitored BMD levels in the distal radius (the wrist joint) and the distal tibia (the ankle joint), among other parts of the body. When compared to women taking the placebo, the study found “exemestane worsens age-related decreases in bone mineral density by about three times, even in the setting of adequate calcium and vitamin D intake,” nutrients which promote bone health.

Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, agrees with the study authors and the accompanying editorial that it is best to be cautious about using exemestane and other aromatase inhibitors for primary breast cancer prevention.

“In this study, they have not proven an increase in actual fractures, but if exemestane accelerates bone loss, then the possibility exists that it also increases the risk of fractures, which for older women can be debilitating and painful. The problem is, we do not yet know about the long term side effects of these drugs in women who would take them to prevent breast cancer.”

He also highlights another observation.

“We have to consider that this study only followed women for two years, but the treatment is supposed to go for five. Doctors and patients would likely be concerned about that amount of bone loss seen in a fairly short time in an otherwise healthy woman.”

Dr. Lichtenfeld wrote cautiously in his June blog entry about a study presented during the 2011 American Society of Clinical Oncology meeting which touted the preventive benefits of exemestane.  He says for women who are at high risk, where breast cancer prevention strategies need to be considered, the treatment may be very beneficial.

“No-one is saying, ‘Do not use it,”’ Dr. Lichtenfeld explains, noting the drug is currently approved by the FDA for the treatment of postmenopausal women with estrogen-receptor positive early breast cancer following surgery to prevent the cancer from returning, or for women whose disease has progressed.

“The Lancet article and editorial suggest that you have to be very careful to understand the long term safety profile of this drug, and weigh the benefits and potential harms when used as a breast cancer prevention option.  In that circumstance, many women who would take the drug never would have developed cancer in the first place; for these women it could potentially do more harm than good.”

Bald Barbie Demand is an Over-Reach – UPDATED

I want to sincerely apologize for the pain my post, which I have now removed, has caused. Like many other committed staff members and volunteers at the American Cancer Society, I have lost loved ones to cancer, and I work here because I want to help end the suffering caused by the disease. But losing a child to cancer (or for any other reason) is unimaginable to me. The idea of having one of my children diagnosed with cancer is a pain I cannot comprehend. I am sorry for making anybody feel marginalized. It was not what I intended. It is not how I feel.

When I set out to write I wanted to raise questions about activism and social media around disease. I did not mean to imply that I or the American Cancer Society believe that sick children are not important. Indeed I wrote that each of these cases is tragic, and that the children and their families deserve both sympathy and support. That is what I believe.

I am committed to repairing the relationship between the advocates I have upset and the American Cancer Society. The idea that my words would cause people to lose faith in the good work of the Society is horrifying to me. The Society succeeds because of our more than three million volunteers, and because of millions of others who generously support our work. In my more than four years working at ACS I have seen one example after another of this organization’s incredible mission being carried out, and each time, I am inspired. I have also seen success that extends to all of us, as cancer incidence and death rates continue to drop. I hope I have not jeopardized the good will that makes this progress possible.

Andrew Becker

Underarm Products and Breast Cancer: Do They or Don’t They?

A new study detected parabens, a chemical used as a preservative in many cosmetics, in the breast tissue of 40 women who underwent mastectomy for breast cancer. Why is that important? Some have claimed parabens in underarm products might raise the risk for breast cancer, based on evidence the compounds may have weak estrogen-like effects, and estrogen is known to play a central role in breast cancer.

But here was the study’s kicker: researchers also found paraben compounds in the seven women who said they’d never used underarm products, leading a study co-author to say in the journal press release:

“Our study appears to confirm the view that there is no simple cause and effect relationship between parabens in underarm products and breast cancer”

Media outlets seemed understandably perplexed about what to conclude. While many seemed to issue a sigh of relief, others were more skeptical. Time Healthland blogger Laura Blue mischievously said the study “may help to alleviate concerns about underarm products further — or rekindle the worry.”

Why the caution in sending out the “all clear?” The study was not designed to answer the question definitively, so it couldn’t make that conclusion.  Here’s what Michael J. Thun, vice president emeritus of the ACS’s Epidemiology and Surveillance Research department told us.

“I think that the press release misinterprets the point of the study. Its purpose was not to study whether parabens (in general) or underarm deodorants (in particular) affect breast cancer risk. Rather, it examined the levels and anatomic distribution of various paraben compounds in the excised breasts of 40 women with breast cancer. At least one form of parabens was detected in all except two of the 160 samples tested, with at least one sample testing positive in all women. This result could not be compared to breast tissue from women without breast cancer, however, since they don’t have mastectomies.

“The first author acknowledges that the study does not show an association between parabens and breast cancer risk in his quote, ‘The fact that parabens were detected in the majority of the breast tissue samples cannot be taken to imply that they actually caused breast cancer in the 40 women studied.’

“Rather, the study merely confirms earlier, smaller studies which detected parabens in breast tissue of women with cancer. It shows that parabens can be absorbed (probably from personal care products) and the underarm deodorant is not the only source.”

Virtually every media outlet pointed out that the most important lesson from the study was that the high rate of the presence of parabens justifies further investigation.

You can read more about the issue on our website.

Why Nicotine Gum and Patches Aren’t Helping Smokers Quit

A study this week had disappointing news about nicotine replacement therapy, or NRT. A long term study by researchers at the Center for Global Tobacco Control at Harvard School of Public Health, published in the journal Tobacco Control, followed nearly 800 smokers who had recently quit smoking for five years. They had them fill out surveys three times during those years. Each time, the surveys showed one in three former smokers had relapsed, and it barely mattered what method they used, including going cold turkey. In other words, while nicotine replacement is pretty good at helping people quit over the short term, over time the lure of tobacco is too strong.

We asked Tom Glynn, Ph.D. director of science and trends, what he thought the study tells us.

“I’m not surprised at the results of this study, because evidence is accumulating that smokers who use NRT do not often use it as directed, nor do they use it long enough to stave off relapse, suggesting that we need to better educate NRT users and the physicians and pharmacists who recommend it.

“We also need to consider recent evidence that shows that NRT for many people is more effective when used longer than the 12 weeks currently on the package inserts, and convince the FDA to modify its current recommendation so that it will  be maximally effective.

“I’m a bit more surprised at the authors’ conclusion (although it’s an argument that has been around for years) that ‘…increasing individual treatment coverage should not be at the expense of population evidence-based programs and policies.’

“The tobacco control field needs to stop acting as if it is involved in a zero-sum game and instead advocate for comprehensive tobacco control approaches that include BOTH individual and population based approaches. In other words, we need to make support available to help smokers quit and work to change the environment around them to make relapsing (or starting smoking) harder.

“The data are very clear that this is what works and that it is cost-effective. Our advocacy activities should reflect that and not pit one approach against another.”

Cancer in Teens and Young Adults: Not Much Improvement?

Our annual Cancer Statistics report garnered plenty of media interest this week, finding that death rates continue to drop. But one story from CBS News caught our eye. It said

“We are making progress in the fight against cancer. The American Cancer Society said Wednesday that death rates are going down. Between 2004 and 2008, they dropped 1.8 percent each year for men and 1.6 percent for women. However, CBS News medical correspondent Dr. Jon LaPook reports there has not been much improvement for teens or young adults….

“Adolescents and young adults aged 15-to-39 account for more than 72,000 new cancers every year — seven times more than pediatric cancers. Unlike other groups, their mortality rates have not improved.”

It is true that young adult cancers have been cancer medicine’s forgotten population, as outlined in an excellent article in our journal, CA: A Cancer Journal for Clinicians by Archie Bleyer back in 2007.

But the claim that mortality rates have not improved is perplexing.

Our epidemiologists heard the CBS report and ran the numbers. Here’s a chart.

The data show despite the challenges facing this population, the overall cancer death rate among people 15 to 39 has decreased by over 50% since 1969.

I asked CBS about the statement, and it turns out what CBS meant to say was that survival rates had not improved.

So what do survival data show? While it is true the improvement in 5-year survival rates over time has been the lowest for ages 15-39 years, 5-year survival in 2001-2007 (81.5%) is similar to that among children (80.4%) and is 17.4% higher than those ages 40 and up (64.1%). It turns out, and this was news to me, that the survival rate in 1977 was already relatively high: 71.1% in adolescents and young adults compared to 58.1% in children and 47.4% in those 40 and older in that same time period. So it had less room to grow.

But using  survival rates is not the best way to measure progress anyway. They can be affected by factors, like increased screening rates, that do not reflect true improvements. In fact mortality rates, a person’s chances of dying of cancer (which we assume is what CBS thought it was reporting) remain the gold standard in marking progress. And death rates, as we saw above, are dropping in young adults.

The unique difficulties facing young adults with cancer is a real issue that demands our attention. The problem is dramatic and serious. It doesn’t require exaggeration.