Mortality from colorectal cancer remains a public-health concern, being the second leading cause of cancer-related death for men and women combined. The major preventive measure for colorectal cancer is to screen for and remove adenomatous polyps. Average-risk individuals (ie, those who do not have a hereditary colorectal syndrome) are offered several screening options starting at age 50 at regular intervals: colonoscopy every 10 years, flexible sigmoidoscopy every 5 years, fecal occult blood test yearly, and computed tomographic colonography every 5 years.

Sigmoidoscopy Study

As reviewed in this issue of The ASCO Post, Holme and colleagues recently reported the results of a large randomized trial of colorectal cancer screening in Norway, comparing the effect of a one-time flexible sigmoidoscopy (with or without fecal occult blood test) with no screening on the incidence and mortality of colorectal cancer after 11 years of follow-up.¹ Participants with an abnormal screening result were offered a colonoscopy. In an intention-to-treat analysis (ie, including the one-third of patients who were invited to be screened but did not participate), flexible sigmoidoscopy screening reduced this incidence and mortality by 20% and 27%, respectively. It is estimated that the absolute reduction of colorectal cancer risk at 10 years would double if all patients adhered to the screening recommendations. Fecal occult blood test did not improve outcomes beyond flexible sigmoidoscopy alone.

Practice Implications and Limitations

The results of this study are in accordance with those reported in three prior large randomized trials of flexible sigmoidoscopy screening (UK Flexi-Scope Trial, Italian SCORE Trial, and U.S. PLCO trial),^2-4 highlighting the effectiveness and safety of this relatively inexpensive method to prevent colorectal cancer and decrease cancer-associated mortality. However, despite these results, flexible sigmoidoscopy screening is underutilized in the United States, and colonoscopy has become the most recommended and performed procedure for colorectal cancer screening. Other screening methods are usually offered to patients who decline colonoscopy, who have severe comorbidities, who do not have access to colonoscopy, or who are underinsured or uninsured. Several factors have contributed to colonoscopy becoming the preferred screening method.

In 2001, Medicare began paying for colonoscopy to screen average-risk individuals, and private insurers followed. Gastroenterologists now had an economic incentive to recommend colonoscopy over other screening tests, and training in flexible sigmoidoscopy by nongastroenterologists (primary-care physicians and internists) has sharply declined. Even though the American College of Physicians and the U.S. Preventive Task Force do not favor one screening method over another, several specialty societies such as the American College of Gastroenterology recommend colonoscopy as the preferred colorectal cancer screening test.^5-8 Although the National Polyp Study group showed that colonoscopic polypectomy provided a 53% reduction in cancer mortality compared with the general population (Surveillance, Epidemiology, and End Results database),⁹ there is no randomized trial level evidence that screening colonoscopy of the general population reduces cancer-related mortality.

The perception of the superiority of colonoscopy as a screening test by the public and health-care providers is largely based on the fact that it is a procedure that allows the visualization of the entire colon (with experts comparing the performance of a screening sigmoidoscopy as opposed to a full colonoscopy with that of mammography on one breast) and is both diagnostic and therapeutic. However, one of the most important arguments for colonoscopy are data from large cohort average-risk patients (mainly males, in the Veterans Affairs Cooperative Study), suggesting that approximately 50% of advanced neoplasia (adenomas larger than 1 cm, villous adenomas, adenomas with high-grade dysplasia, or colorectal cancer) proximal to the splenic flexure would be missed if the initial screening strategy relied on sigmoidoscopy (with colonoscopy only performed if a distal adenoma is detected on sigmoidoscopy).

The issue seems to be even more relevant in women. A large cohort study of screening colonoscopy for average-risk women showing that up to 65% of proximal advanced neoplasia would have been missed if the initial screening test was limited to sigmoidoscopy.^10,11

Further Considerations

What we are certain of is that any screening is better than no screening at all and that there might not be a gold standard test that applies to all patients. Beyond defining which screening tool is optimal in decreasing the incidence and related mortality of colorectal cancer, a more important issue to be addressed is the fact that colorectal cancer screening rates remain low (less than 50% of average-risk individuals undergo screened) despite the many test options available to patients.¹²

A screening test that examines the entire colon, that is not invasive like an endoscopy, that is easy to perform and not time-consuming, and that is cost-effective would be an ideal screening tool for patients and physicians alike. The multitarget stool DNA test (which also includes a hemoglobin immunoassay) has the potential to become such a screening tool.  Compared with colonoscopy, stool DNA testing has a sensitivity of 92% and 42% for detecting colorectal cancer and advanced adenomas, respectively.¹³

Hence, the debate between screening sigmoidoscopy followed by colonoscopy only if a distal adenoma is found vs initial screening colonoscopy might soon become a thing of the past, with the recent U.S. Food and Drug Administration approval of stool DNA testing for colorectal cancer screening. Physicians and professional societies will need to define the role of this new technology and include it in our strategy to improve colorectal cancer screening compliance and reduce the incidence and mortality of colorectal cancer. ■

Disclosure: Dr. Charabaty reported no potential conflicts of interest.

References

1. Holme Ø, et al: Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality.  JAMA 312:606-615, 2014.

2. Atkin WS, et al: Lancet 375:1624-1633, 2010.

3. Segnan N, et al: Once-only sigmoidoscopy in colorectal cancer screening. J Natl Cancer Inst 103:1310-1322, 2011.

4. Schoen RE, et al: Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med 366:2345-2357, 2012.

5. Qaseem A, et al: Screening for colorectal cancer. Ann Intern Med 156:378-386, 2012.

6. U.S. Preventive Services Task Force: Screening for colorectal cancer. Ann Intern Med 149:627-637, 2008.

7. Rex DK, et al: American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected].  Am J Gastroenterol 104:739-750, 2009.

8. Levin B, et al: Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008. Gastroenterology 134:1570-1595, 2008.

9. Zauber AG, et al: Colonoscopic polypectomy and long-term prevention of colorectal-cancer death. N Engl J Med 366:687-696, 2012.

10. Lieberman DA, et al: Use of colonoscopy to screen asymptomatic adults for colorectal cancer. N Engl J Med 343:162-168, 2000.

11. Schoenfeld P, et al: Colonoscopic screening of average-risk women for colorectal neoplasia. N Engl J Med 352:2061-2068, 2005.

12. Swan J, et al: Progress in cancer screening practices in the United States. Cancer 97:1528-1540, 2003.

13. Imperiale TF, et al: Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med 370:1287-1297, 2014.

Dr. Charabaty is Director of the Center for Inflammatory Bowel Diseases at Georgetown University Hospital, Washington, DC.