Although cancer death rates have been dropping since the publication of the first Annual Report to the Nation 10 years ago, the latest edition marks the first time the report has documented a simultaneous decline in cancer incidence, the rate at which new cancers are diagnosed, for both men and women. Based on the long-term incidence trend, rates for all cancers combined decreased 0.8 percent per year from 1999 through 2005 for both sexes combined; rates decreased 1.8 percent per year from 2001 through 2005 for men and 0.6 percent per year from 1998 through 2005 for women. The decline in both incidence and death rates for all cancers combined is due in large part to declines in the three most common cancers among men (lung, colon/rectum, and prostate) and the two most common cancers among women (breast and colon/rectum), combined with a leveling off of lung cancer death rates among women.

“The drop in incidence seen in this year’s Annual Report is something we’ve been waiting to see for a long time,” said Otis W. Brawley, M.D., chief medical officer of the American Cancer Society (ACS). “However, we have to be somewhat cautious about how we interpret it, because changes in incidence can be caused not only by reductions in risk factors for cancer, but also by changes in screening practices. Regardless, the continuing drop in mortality is evidence once again of real progress made against cancer, reflecting real gains in prevention, early detection, and treatment.”

The new report shows that, from 1996 through 2005, death rates for all cancers combined decreased for all racial and ethnic populations and for both men and women, except for American Indian/Alaska Native men and women, for whom rates were stable. The drop in death rates has been steeper for men, who have higher rates, than for women. Death rates declined for 10 of the top 15 causes of cancer death among both men and women. However, death rates for certain individual cancers are increasing, including esophageal cancer for men, pancreatic cancer for women, and liver cancer for both men and women. Overall cancer death rates were highest for African-Americans and lowest for Asian American/Pacific Islanders.

Among men, incidence rates dropped for cancers of the lung, colon/rectum, oral cavity, and stomach. Prostate cancer incidence rates decreased by 4.4 percent per year from 2001 through 2005 after increasing by 2.1 percent per year from 1995 to 2001. In contrast, incidence rates increased for cancers of the liver, kidney, and esophagus, as well as for melanoma (2003-2005), non-Hodgkin lymphoma, and myeloma. Incidence rates were stable for cancers of the bladder, pancreas, and brain/nervous system, and for leukemia.

For women, incidence rates dropped for cancers of the breast, colon/rectum, uterus, ovary, cervix, and oral cavity but increased for cancers of the lung, thyroid, pancreas, brain/nervous system, bladder, and kidney, as well as for leukemia, non-Hodgkin lymphoma, and melanoma.

“While we have made progress in reducing the burden of cancer in this country, we must accelerate our efforts, including making a special effort to reach underserved cancer patients in the communities where they live,” said National Cancer Institute (NCI) Director John Niederhuber, M.D. “This report gives us a better understanding of where we may need to redouble our efforts and try to find new ways of preventing or reducing the occurrence of kidney, liver, and other cancers that continue to show increases in both mortality and/or incidence.”

The Special Feature section of the Report highlights wide variations in tobacco smoking patterns across the United States, which, coupled with differences in smoking behaviors in younger versus older populations, helps explains the delay in an expected decrease in lung cancer deaths among women and a slowing of the decrease in lung cancer deaths among men.

The report finds substantial differences in lung cancer death rate trends by state and geographic region. For example, lung cancer death rates dropped an average of 2.8 percent per year among men in California from 1996 through 2005, more than twice the drop seen in many states in the Midwest and the South. The geographic variation is even more extreme among women, for whom lung cancer death rates increased from 1996 through 2005 in 13 states and decreased only in three. The report also notes that, in five states (Pennsylvania, Illinois, Minnesota, Nebraska, and Idaho), lung cancer incidence among women showed an increasing trend, whereas the mortality trend was level.

“It’s very promising to see the progress we are making in our fight against cancer,” said Centers for Disease Control and Prevention (CDC) Director Julie Gerberding, M.D. “Unfortunately, tobacco use continues to plague our country, and it’s the primary reason why lung cancer continues to rob too many people of a long, productive, and healthy life. We must recommit ourselves to implementing tobacco control programs that we know work if we are truly going to impact the staggering toll of tobacco on our society.”

Variation in smoking prevalence among the states is influenced by several factors, including public awareness of the harms of tobacco use, social acceptance of tobacco use, local tobacco control activities, and tobacco industry promotional activities targeted in a geographic area. The 13 states where lung cancer death rates for women are on the rise have higher percentages of adult female smokers, low excise taxes, and local economies that are traditionally dependent on tobacco farming and production. In contrast, California, which was the first state to implement a comprehensive, statewide tobacco control program, was the only state in the country to show declines in both lung cancer incidence and deaths in women.

According to a U.S. Surgeon General’s report, cigarette smoking accounts for approximately 30 percent of all cancer deaths, with lung cancer accounting for 80 percent of the smoking-attributable cancer deaths. Other cancers caused by smoking include cancers of the oral cavity, pharynx, larynx, esophagus, stomach, bladder, pancreas, liver, kidney, and uterine cervix and myeloid leukemia.

“We can see that, in areas of the country where smoking and tobacco use are entrenched in daily life, men and women continue to pay a price with higher incidence and death rates from many types of cancer. This type of geographic variation in smoking-related cancers is due to smoking behaviors, not regional environmental factors,” said Betsy A. Kohler, M.P.H., executive director of the North American Association of Central Cancer Registries (NAACCR).

“The observed decrease in the incidence and death rates from all cancers combined in men and women overall and in nearly all racial and ethnic groups is highly encouraging,” conclude the authors. “However, this must be seen as a starting point rather than a destination.” They say a dual effort, combining better application of existing knowledge with ongoing research to improve prevention, early detection, and treatment will be needed to sustain and extend this progress into the future.

The study was conducted by scientists at the ACS, CDC, NCI, which is part of the National Institutes of Health, and the NAACCR.

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Jemal A, Thun MJ, Ries LAG, Howe HL,Weir HK, Center MM, Ward E, Wu X, Eheman C, Anderson R, Ajani U, Kohler B, Edwards BK. Annual Report to the Nation on the Status of Cancer, 1975-2005, Featuring Trends in Lung Cancer, Tobacco Use and Tobacco Control. Journal of the National Cancer Institute; Published online Nov. 25, 2008; Print issue Dec. 2, 2008. Vol. 100, No. 23.

To view the full report, go to: http://jnci.oxfordjournals.org/cgi/content/full/djn389?ijkey=7gzxMw78EFM11MN&keytype=ref.

For a Q&A on this Report, go to http://cancer.gov/newscenter/pressreleases/ReportNation2008QandA.

For Spanish translations of this press release and Q&A, go to http://cancer.gov/espanol/noticias/ReportNation2008SpanishRelease.

ACS: http://www.cancer.org.

CDC’s Division of Cancer Prevention and Control: http://www.cdc.gov/cancer.

NAACCR: http://www.naaccr.org.

NCI: http://www.cancer.gov and the SEER Homepage: http://www.seer.cancer.gov.

The Data Monitoring Committee overseeing the trial (known as E1900, clinical trial registry number NCT00049517) recommended that the results of a recent interim analysis be made public because the study had met its primary endpoint of demonstrating improved overall survival. Researchers found that the patients in the trial who received the higher dose of daunorubicin (90 milligrams per square meter of body surface area, or 90mg/m², given on each of the first three days of treatment) in combination with standard treatment of a chemotherapy drug used for AML since the 1960s, ara-C (cytarabine), had a median overall survival of 23.7 months compared to patients treated with the standard dose of daunorubicin (45 mg/m² given on each of the first three days of treatment) in combination with ara-C, who had a median overall survival of 15.1 months. This survival difference was highly statistically significant. Also of importance, the frequency of serious treatment toxicities observed in this study was similar between the high-dose and standard-dose daunorubicin treatment groups.

“The findings of this large clinical trial are important because they will likely change practice and improve the outcome for many patients with AML,” said Martin Tallman, M.D., chair of the ECOG Leukemia Committee and professor of Medicine at Northwestern University Feinberg School for Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago. The trial’s study chair was Hugo Fernandez, M.D., associate professor of Medicine and Oncology and associate chief of the Blood & Marrow Transplantation Division at the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla.

A total of 633 patients with non-promyelocytic AML who had not previously received chemotherapy were enrolled in this study between December 2004 and September 2008. Patients were randomly assigned to one of two treatment groups to receive initial, or induction, chemotherapy with either high-dose or standard-dose daunorubicin with ara-C. Patients who were assessed as having a complete, positive response to induction therapy were then treated with additional therapy. As of September 2008, 334 patients proceeded to the next, or consolidation step of the study.

Bone marrow transplantation and peripheral blood stem cell transplantation are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy and are common procedures for patients with AML. In this trial, those patients with unfavorable prognostic factors and/or matching sibling donors were treated with an allogeneic (donor) transplant whenever possible. Among those who received standard-dose daunorubicin, 4.7 percent underwent allogeneic hematopoietic stem cell transplantation (HSCT). For those randomized to high-dose daunorubicin, 5.7 percent underwent allogeneic HSCT. There were no differences between the treatment groups in terms of subsequent chemotherapy or autologous transplantation that affect the results of the trial.

Because daunorubicin is an FDA-approved drug for AML, patients with this disease can potentially gain immediate benefit from the results of this trial. “This trial is a prime example of a study question that would only have been carried out by an NCI-sponsored oncology Cooperative Group because the agent tested in the trial has been in common use for this disease for more than three decades and there’s little incentive for commercial concerns to test an already approved product,” said James H. Doroshow, M.D., director of NCI’s Division of Cancer Treatment and Diagnosis.

An estimated 13,290 people will be diagnosed with AML in the United States in 2008. Most cases are in adults with half the cases being under 60 years of age. Overall, only about 33 percent of those with AML survive the disease, and survival is less likely with increasing age. Advances in AML therapy depend in large part on the ability to increase the initial response to induction therapy.

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E1900: A Phase III Trial in Adult Acute Myeloid Leukemia: Daunorubicin Dose-Intensification prior to Risk-Allocated autologous Stem Cell Transplantation. The full protocol for this trial can be found at http://www.cancer.gov/clinicaltrials/ECOG-1900.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The Southwest Oncology Group (SWOG), an international network of research institutions, coordinates SELECT at more than 400 clinical sites in the United States, Puerto Rico, and Canada.

Data and additional analyses of the SELECT trial were published online December 9, 2008, in JAMA. Among the specific results highlighted, the five-year rate of prostate cancer diagnosis in the four arms of the study was 4.43 percent in the placebo arm of the trial, 4.56 percent in the selenium arm, 4.93 percent in the vitamin E arm (the highest rate, but one that does not show a statistically significant difference from the placebo arm), and 4.56 percent in the selenium plus vitamin E arm.

Adherence to the study protocol dropped off from year one to year five (83 percent adherent vs. 65 percent at year five), which was expected and did not affect the trial outcome.

SELECT participants received letters in October 2008 explaining the study review and telling them to stop taking their study supplements. Participants will continue to have their health monitored by study staff, which may include regular digital rectal exams and PSA (prostate-specific antigen) tests to detect prostate cancer. Investigators intend to follow the participants for about three years to determine the long-term effects of having taken either supplement or placebo and to complete a biorepository of blood samples that will be used in extensive molecular analyses to give researchers a better understanding of prostate cancer, other cancers, and other diseases of male aging. This additional data collection is a vital part of the study.

Neither the men nor their physicians know which supplements or placebos the men have been taking, a procedure known as blinding or masking. As followup of the SELECT participants continues, the participants will continue to be blinded. A blinded followup may avoid unintentional bias and potentially false conclusions. However, at the request of a participant, they will be informed which supplement, if any, they received.

“SELECT was always designed as a study that would answer more than a single question about prostate cancer,” said Eric Klein, M.D., a study co-chair for SELECT, and a physician at the Cleveland Clinic. “As we continue to monitor the health of these 35,000 men, this information may help us understand why two nutrients that showed strong initial evidence to be able to prevent prostate cancer did not do so.”

SELECT was undertaken to substantiate earlier, separate findings from studies in which prostate cancer was not the primary outcome: a 1998 study of 29,133 male smokers in Finland who took vitamin E to prevent lung cancer surprisingly showed 32 percent fewer prostate cancers in men who took the supplement, and a 1996 study of 1,312 men and women with skin cancer who took selenium for prevention of the disease showed that men who took the supplement had 52 percent fewer prostate cancers than men who did not take the supplement.

Based on these and other earlier findings, in 2001, men were recruited to participate in SELECT. They were randomly assigned to take one of four sets of supplements or placebos, with more than 8,000 men in each group. One group took both selenium and vitamin E; one took selenium and a vitamin E placebo; one took vitamin E and a selenium placebo; and the final group received placebos of both supplements.

It should be noted that in 2003, while SELECT was recruiting men, a different SWOG-sponsored study reported that the drug finasteride reduced the incidence of prostate cancer by 25 percent. When this was discovered, men on SELECT were informed and allowed to take finasteride (4.8 percent of men, not on the other SWOG study, took the drug at some time during the SELECT trial). Finasteride has not yet been approved by the U.S. Food and Drug Administration for prostate cancer prevention.

Except for skin cancer, prostate cancer is the most common type of cancer in men in the United States. In 2008, there will be an estimated 186,320 new cases of prostate cancer and 28,660 deaths from this disease in the United States. “Finding methods to prevent and treat prostate cancer remains a priority for the NCI, and with the aid of new molecular diagnostic tools and applications, we hope to continue to make headway in reducing deaths and new cases of this disease,” said NCI director John E. Niederhuber, M.D. “The science of cancer prevention is also leading toward individualized, molecular prevention, in which we will calculate risk and design preventive steps based on an individual’s genome.”

SELECT has been funded by NCI for $114 million, with additional monies from the National Center for Complementary and Alternative Medicine, and with substudies funded and conducted by the National Heart, Lung and Blood Institute, the National Institute of Aging and the National Eye Institute at NIH. The substudies were evaluating the effects of selenium and vitamin E on chronic obstructive pulmonary disease, the development of Alzheimer’s disease, and the development of macular degeneration and cataracts, and will continue without participants taking study supplements. An NCI-funded substudy is looking at the effects of the supplements on men who developed colon polyps.

“The SELECT trial owes a tremendous debt to our volunteers, the thousands of men who offered their time and enthusiastic participation, all in the interest of a future when prostate cancer can be prevented,” said Laurence H. Baker, D.O., chairman of the Southwest Oncology Group. SELECT investigators are analyzing the data and will submit the analysis for publication in a peer-reviewed medical journal.

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Reference: Lippman SM, Klein EA, Goodman PJ, et al. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers. JAMA. Published online December 9, 2008.

For a Q&A on SELECT, please go to http://www.cancer.gov/newscenter/pressreleases/SELECTQandA.

For a Spanish version of the release and Q&A, please go to http://www.cancer.gov/espanol/noticias/SELECTresults2008spanish.

The Southwest Oncology Group (www.swog.org) is one of the largest cancer clinical trials cooperative groups in the United States. Funded by research grants from the National Cancer Institute, part of the National Institutes of Health, the group conducts clinical trials to prevent and treat cancer in adults, and to improve the quality of life for cancer survivors. The group’s network of more than 5,000 physician-researchers practice at nearly 550 institutions, including 18 National Cancer Institute-designated cancer centers. Headquartered in Ann Arbor, Mich. (734-998-7130), the group has an operations office in San Antonio, Tex. and a statistical center in Seattle, Wash.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Using easily obtainable information (e.g. personal and family medical history, lifestyle behaviors, and age), the tool provides an estimate of an individual’s risk of developing colorectal cancer over certain time periods (within five years, 10 years and over the course of a lifetime). This risk-assessment model is the first to provide an absolute risk estimate for colorectal cancer (i.e. the probability of developing colorectal cancer over a given period of time) for the general, non-Hispanic white population age 50 or older in the United States.

“Much like the NCI’s breast cancer and melanoma risk assessment tools, this new colorectal cancer risk assessment tool should prove useful not only in counseling patients on their individual risk, but also in helping plan type and frequency of screening intervention studies,” said NCI Director John E. Niederhuber, M.D. “As we move toward an era of personalized medicine, the ability to assess an individual patient’s cancer risk and thereby improve our ability to apply appropriate prevention measures is of vital importance.”

Approximately one in 18 Americans will develop colorectal cancer at some point during his or her lifetime. In 2008, an estimated 148,810 people will be diagnosed with colorectal cancer in the United States and another 49,960 will die of the disease. There are several screening options for colorectal cancer, including fecal occult blood tests (which look for the presence of blood in stool samples), sigmoidoscopy (which uses a lighted probe to inspect the sigmoid, or lowest part, of the colon), colonoscopy (which uses a lighted probe to inspect the entire colon), and computerized tomographic colonography, also known as virtual colonoscopy (which uses CT scans, a type of x-ray, to create images of the entire colon). Having additional information about an individual’s risk could aid health care providers and their patients in making decisions about which screening regimen to pursue.

To develop the risk-assessment model, researchers used data from two large population-based case-control studies. Several factors that have been previously associated with colorectal cancer risk were shown to be predictive of a colorectal cancer diagnosis in those two studies, including age; family history of colorectal cancer; consumption of vegetables; body mass index; cigarette smoking; use of aspirin or other non-steroidal anti-inflammatory drugs; physical activity; use of hormone replacement therapy; previous history of sigmoidoscopy and/or colonoscopy; and history of polyps. Estimates of relative risk (comparisons of risk in one group to another) from the case-control studies were combined with population-based data on colorectal cancer incidence from NCI’s SEER (Surveillance, Epidemiology and End Results) cancer registries to make the model broadly applicable in the United States.

“This colorectal cancer risk model should provide physicians and their patients a new tool to help make informed decisions about cancer screening and other cancer prevention strategies. It may also assist policy makers in evaluating the usefulness of current and future population colorectal cancer screening approaches,” said Andrew Freedman Ph.D., lead author of the paper which describes the development of the risk-assessment model.

To test the accuracy of the risk-assessment model, the researchers compared expected numbers of colorectal cancer cases predicted by the model to the observed numbers of cases identified in the NIH-AARP Diet and Health Study, a large study that follows AARP members and collects information about nutrition and health. From information about individual risk factors that was collected when participants entered the study, the researchers used the new model to estimate the number of men and women who would be expected to develop colorectal cancer. According to Ruth Pfeiffer, Ph.D., who was the senior author of the validation study, “The colorectal cancer risk-assessment tool predicted the numbers of colorectal cancer diagnoses well overall, and in most risk categories.”

Because the majority of participants in the two case-control studies used to develop the model were non-Hispanic whites age 50 or older, the researchers were unable to estimate relative risks for other age and racial/ethnic groups. However, there are plans to expand the tool to include these populations in the future. In addition, the tool is not applicable to individuals with certain gastrointestinal disorders (such as ulcerative colitis or Crohn’s disease), certain inherited genetic conditions (such as familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer) or a personal history of colorectal cancer. These conditions are known to carry a very high risk of developing colorectal cancer.

In addition to the standard Web tool, a mobile Web-based version for use on Internet-enabled mobile devices and the source code for the model will soon be made available to researchers. It is important that users of the online tool work with their primary health care provider to interpret the results and plan a course of action regarding colorectal cancer screening.

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NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Freedman AN, Slattery ML, Ballard-Barbash R, Willis G, Cann BJ, Pee D, Gail MH, and Pfeiffer RM. A Colorectal Cancer Risk Prediction Tool for White Men and Women Without Known Susceptibility. JCO. Online December 29, 2008.

Park Y, Freedman AN, Gail MH, Pee D, Hollenbeck A, Schatzkin A, and Pfeiffer RM. Validation of a Colorectal Cancer Risk Prediction Model among Whites 50 Years Old and Over. JCO. Online December 29, 2008.

To view the new Colorectal Cancer Risk Tool online, please visit: http://www.cancer.gov/colorectalcancerrisk

For more information on understanding cancer risk, please visit: http://understandingrisk.cancer.gov