The long-term incidence of colorectal cancer was lower in patients who underwent screening by either endoscopy or fecal occult-blood testing than in those who did not, even if that screening took place decades earlier, according to two separate reports published online Sept. 19 in the New England Journal of Medicine.
Importantly, colorectal cancer–related mortality also was correspondingly lower in screened patients.
Identifying and removing colorectal polyps yields far-reaching benefits, saving lives for up to 30 years afterward, researchers involved in both studies said.
Dr. Aasma Shaukat
In the first study, Reiko Nishihara, Ph.D., of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and her associates assessed lower-GI endoscopy’s effect on the long-term risk of incident colorectal cancer in two large U.S. cohorts that were prospectively followed for 22 years. The Nurses’ Health Study involved 121,700 female nurses aged 30-55 years at baseline in 1976, and the Health Professionals Follow-Up Study involved 51,529 male health professionals aged 40-75 years at baseline in 1986.
For their secondary analysis of data from these cohorts, Dr. Nishihara and her colleagues examined the records of 57,166 female subjects and 31,736 male subjects who developed 1,815 incident colorectal cancers during 22 years of follow-up. "We were able to directly compare actual incidences of cancer among persons after polypectomy with the incidences among persons from the same background population who did not undergo endoscopy, while adjusting for potential confounders."
At their own discretion, 14,287 of the men and 31,423 of the women had undergone no lower endoscopy at all by 1998, the midpoint of follow-up; 3,578 men and 3,957 women had undergone colonoscopy with negative results; 8,091 men and 16,748 women had undergone sigmoidoscopy with negative results; and 1,259 men and 1,481 women had undergone lower endoscopy with polypectomy.
At the end of follow-up, the incidence of colorectal cancer was significantly lower among the men and women who had undergone any of these screening methods than among those who had not had any screening. The multivariate hazard ratios for colorectal cancer were 0.57 after endoscopy plus removal of adenomatous polyps (polypectomy), 0.60 after negative sigmoidoscopy, and 0.44 after negative colonoscopy.
"We estimated that 40% of colorectal cancers (including 61% of distal colorectal cancers and 22% of proximal colon cancers) that developed during follow-up would have been prevented if all the participants in our study had undergone colonoscopy," the investigators said (N. Engl. J. Med. 2013 Sept. 19 [doi:10.1056/NEJMoa1301969]).
This decrease in colorectal cancer occurred in both men and women, across all stages of disease at presentation, and regardless of subject age, body mass index, smoking status, or use of aspirin prophylaxis.
"Negative colonoscopy was associated with a lower incidence of both distal colorectal cancer and proximal colon cancer, whereas negative sigmoidoscopy and colonoscopy with polypectomy were associated primarily with a lower incidence of distal colorectal cancer," they said.
Notably, screening sigmoidoscopy and screening colonoscopy were associated with lower colorectal cancer–specific mortality, compared with no endoscopy.
The association between a negative colonoscopy and a significantly reduced incidence of colorectal cancer persisted for up to 15 years after the procedure. Thus, "our findings support the 10-year examination interval recommended by existing guidelines for persons at average risk who have a negative colonoscopy. Our study suggests that even a single negative colonoscopy is associated with a very low long-term risk of colorectal cancer," Dr. Nishihara and her associates said.
Among study subjects who were found to have adenomas, the reduced incidence of colorectal cancer persisted for up to 5 years after the procedure. Thus, "our data support screening at more frequent intervals for persons with a family history of colorectal cancer, which [also] supports current surveillance guidelines."
The researchers also examined DNA from stored specimens of tumors from 62 patients who developed colorectal cancer within 5 years of "passing" an endoscopy. Compared with other cancers, these interval cancers were much more likely to have CpG island methylator phenotype (CIMP), microsatellite instability, and high levels of LINE-1 methylation – all indicators of increased tumor aggressiveness.
It is possible that such lesions are particularly difficult to detect endoscopically or to remove adequately. "It remains unclear whether any of the challenges posed by these biological differences can be addressed by improvements in colonoscopic technique, including more meticulous inspection or improved bowel cleaning," the researchers said.
In the second study, a different research group found that adults who were screened for colorectal cancer using fecal occult blood testing (FOBT) had a 32% decrease in colorectal cancer–related mortality for up to 30 years afterward.