Two studies published in the New England Journal of Medicine showed that patients who underwent screening with endoscopy or fecal occult blood testing had lower rates of distant colorectal cancer than those who did not, even when screening was performed decades earlier. Importantly, colorectal-related mortality was correspondingly lower in screened patients than in unscreened patients. The investigators of both studies said that identifying and removing colorectal polyps had significant benefits and could extend life expectancy by 30 years. In the first study, Reiko Nishihara, MD, PhD, of the Dana-Farber Cancer Institute and Harvard Medical School, and colleagues evaluated the impact of lower GI endoscopy on the long-term risk of incident colorectal cancer in 2 large U.S. cohorts with 22 years of prospective follow-up. The Nurses’ Health Study enrolled 121,700 female nurses aged 30 to 55 years at baseline in 1976, and the Medical Staff Follow-up Study enrolled 51,529 male health professionals aged 40 to 75 years at baseline in 1986. The investigators conducted a secondary analysis of medical record data from 57,166 female subjects and 31,736 male subjects who had 1,815 episodic colorectal cancer cases during the 22-year follow-up period. The investigators determined that by 1998 (the midpoint of follow-up), 14,287 men and 31,423 women had not undergone lower GI endoscopic screening; 3,578 men and 3,957 women had undergone endoscopic screening with negative results; 8,091 men and 16,748 women had undergone sigmoidoscopic screening with negative results; and 1,259 men and 1,481 women had undergone 1,259 men and 1,481 women underwent lower gastrointestinal endoscopic screening and polypectomy. At the end of follow-up, the incidence of colorectal cancer was significantly lower in men and women who underwent any of these screenings than in those who did not undergo any screening. The multifactor risk ratio for colorectal cancer was 0.57 after endoscopy + removal of adenomatous polyps (polypectomy), 0.60 after negative sigmoidoscopy screening, and 0.44 after negative colonoscopy screening. The investigators estimated that if all enrolled subjects had undergone colonoscopy screening, it would have prevented 40% of the colorectal cancers that occurred during follow-up. The researchers estimated that if all enrolled subjects had undergone colonoscopy, it would have prevented 40% of the colorectal cancers that occurred during follow-up (including 61% of distal colorectal cancers and 22% of proximal colon cancers). This reduction in colorectal cancer was observed in men and women at all disease stages at the time of presentation, regardless of subject age, body mass index, smoking status, and prophylactic aspirin use. Negative colonoscopic screening was associated with a lower incidence of distal colorectal and proximal colon cancer, whereas negative sigmoidoscopic screening and colonoscopic screening + polypectomy were primarily associated with a lower incidence of distal colorectal cancer. Notably, sigmoidoscopic and colonoscopic screening were associated with lower colorectal cancer-specific mortality compared with no endoscopic screening. The association between negative colonoscopic screening and a significantly lower incidence of colorectal cancer persisted until 15 years after screening. Thus, the results of this study support the current guideline recommendation of 1 screening visit at 10-year intervals for intermediate-risk individuals with negative colonoscopy screening. This study suggests that even a single negative colonoscopy screening is associated with a very low risk of distant colorectal cancer. In subjects with adenomas, the reduced incidence of colorectal cancer persisted until 5 years after screening. Thus, the study supports both more frequent screening at intervals for individuals with a family history of colorectal cancer and current surveillance guidelines. The researchers also examined DNA from tumor samples collected from 62 patients who developed colorectal cancer within 5 years of endoscopic screening, and cancers at this interval were more likely to have a CpG island methyl subphenotype (CIMP), microsatellite instability and high levels of LINE-1 methylation, all of which are signs of increased tumor aggressiveness, compared with other cancers. Such lesions may be particularly difficult to detect endoscopically or to be adequately resected, the investigators said. It is unclear whether the problems caused by these biological differences could be addressed by improved endoscopic techniques (including more careful examination or improved bowel cleansing). In a second study, Dr. Aasma Shaukat and colleagues at the Minneapolis Veterans Health Care System and the University of Minnesota Minneapolis found that colorectal cancer-related mortality was reduced by 32% in adults screened for colorectal cancer using the fecal occult blood test (FOBT) and that the effect lasted for 30 years thereafter. This association was stronger in men than in women. Researchers conducted a secondary analysis of data from the Minnesota Colon Cancer Control Study. In that study, 46,551 healthy men and women aged 50 to 80 years at baseline from 1975 to 1978 were randomized to annual, 2-year, or no FOBT screening until 1993. The investigators attempted to determine the mortality status and cause of death for as many subjects as possible in 2011, and they found 33,020 deaths, or 71% of the entire study population. A total of 732 deaths were attributed to colorectal cancer. Both annual and 2-year FOBT screening reduced colorectal cancer-specific mortality by 1/3 and the effect lasted up to 30 years after screening. The relative risk of colorectal cancer death was 0.68 in the 1-year FOBT group and 0.78 in the 2-year FOBT group compared with the no FOBT group. overall, the relative risk of death in any FOBT screening group was 0.73 compared with the no FOBT group. this reduction was consistent with the effect of resection of adenomas that progressed to cancer and death. The reduction in colorectal cancer-specific mortality was greater in men than in women. The researchers said that stool-based screening, with its high accessibility and acceptability, has significant implications for improving screening rates in the public, but that this screening method is more frequent than flexible sigmoidoscopy or colonoscopy screening. Dr. Nishihara’s research is supported by the National Institutes of Health, among others, and Dr. Nishihara declares no affiliation with pharmaceutical companies; a colleague declares affiliation with several pharmaceutical companies, including Bayer, and Dr. Shaukat’s research is supported by the Department of Veterans Affairs Performance Review Award Program, among others, and Dr. Shaukat and colleagues declare no financial conflicts of interest. Theodore R. Levin, MD, and Douglas A. Corley, MD, of Kaiser Permanente Medical Center, said the two studies confirm that colonoscopy and FOBT are effective screening methods for colorectal cancer and reaffirm that current screening guidelines are appropriate. However, the two studies, one randomized and the other an observational study of volunteers, were different and the populations were not comparable, so it would be wrong to compare them. Also, both colonoscopy and FOBT techniques have improved since these two studies were conducted. The ongoing randomized study will shed light on the value of colonoscopy versus FOBT, the biology of interstage cancers, and the overall effectiveness of colorectal cancer screening programs. both Dr. Levin and Dr. Corley declare no relevant financial conflicts of interest