Tumor biology appears to play role in missed interval colorectal cancers

ORLANDO – Colorectal cancers that are identified 6 months or more after a colonoscopy due to either a missed lesion or a new cancer development occur in 3.5%-6% of patients in the United States, findings from a large population-based retrospective cohort study suggest.

Characteristics of these missed or newly developed cancers, or "missed interval" cancers, suggest that tumor biology, rather than patient or physician factors, plays an important role in their development, Dr. N. Jewel Samadder said at the annual Digestive Disease Week.

Of 129,936 patients aged 50-80 years who underwent colonoscopy in Utah between Feb. 15, 1995, and Jan. 31, 2009, 2,659 were diagnosed with colorectal cancer, and 37 cases of a missed interval cancer that occurred 6-60 months after the index colonoscopy were identified. Using a 6- to 36-month window following the index colonoscopy, the rate of missed interval cancers was 3.5%; using a 6- to 60-month window, the rate was 6%, said Dr. Samadder of Huntsman Cancer Institute, Salt Lake City.

Nearly 85% of the missed cancers occurred in patients who underwent polypectomy at a prior colonoscopy, meaning only about 15% occurred in patients with a prior clean colonoscopy. Furthermore, missed interval colorectal cancers were significantly associated with a lower stage than were those detected at the index colonoscopy (advanced-stage odds ratio, 0.70), and were significantly more likely to be proximally located (OR, 2.24), he said.

Missed interval cancers also were associated with distinctly better survival than were detected cancers, both overall (hazard ratio, 0.63), and by stage (HR: 0.77, 0.54, 0.50, and 0.48 for cancer stages 1, 2, 3, and 4, respectively), he noted.

The findings are noteworthy because while prior studies from other countries have shown similar rates of missed interval colorectal cancers, those findings weren’t necessarily generalizable to U.S. populations, and the rate in the United States has been unclear, Dr. Samadder said. The size of the current study and the use of statewide data reflect clinical practice and make the findings generalizable to the U.S. population and routine GI clinical practice, he noted.

Although colonoscopy is the preferred screening option for colorectal cancer, controversy exists about its effectiveness, particularly with respect to missed interval cancer, he said.

Several factors have been suggested as to the cause of missed interval cancers, including a low adenoma detection rate, incomplete colonoscopy, poor bowel preparation, and differences in tumor biology.

In this study, neither age nor gender was associated with missed interval versus detected cancer. Also, the cecal intubation rate was 92% in the missed interval cases, and bowel prep was rated as good or excellent in 92% of cases. All procedures were performed by a gastroenterologist.

"Thus, our study suggests that a low adenoma detection rate, incomplete colonoscopy, and poor bowel prep may not be the complete estimation of the missed interval cancer issue; tumor biology may play a greater role," Dr. Samadder said. The results are consistent with missed interval colorectal cancers developing from either microsatellite instability or the serrated pathway, he added.

"Future directions include determining molecular predictors of missed interval colorectal cancer, thus identifying patients and communities at greatest risk and needing increased surveillance," he said.

Dr. Samadder has served as a speaker and teacher for Cook.

ORLANDO – Colorectal cancers that are identified 6 months or more after a colonoscopy due to either a missed lesion or a new cancer development occur in 3.5%-6% of patients in the United States, findings from a large population-based retrospective cohort study suggest.

Characteristics of these missed or newly developed cancers, or "missed interval" cancers, suggest that tumor biology, rather than patient or physician factors, plays an important role in their development, Dr. N. Jewel Samadder said at the annual Digestive Disease Week.

Of 129,936 patients aged 50-80 years who underwent colonoscopy in Utah between Feb. 15, 1995, and Jan. 31, 2009, 2,659 were diagnosed with colorectal cancer, and 37 cases of a missed interval cancer that occurred 6-60 months after the index colonoscopy were identified. Using a 6- to 36-month window following the index colonoscopy, the rate of missed interval cancers was 3.5%; using a 6- to 60-month window, the rate was 6%, said Dr. Samadder of Huntsman Cancer Institute, Salt Lake City.

Nearly 85% of the missed cancers occurred in patients who underwent polypectomy at a prior colonoscopy, meaning only about 15% occurred in patients with a prior clean colonoscopy. Furthermore, missed interval colorectal cancers were significantly associated with a lower stage than were those detected at the index colonoscopy (advanced-stage odds ratio, 0.70), and were significantly more likely to be proximally located (OR, 2.24), he said.

Missed interval cancers also were associated with distinctly better survival than were detected cancers, both overall (hazard ratio, 0.63), and by stage (HR: 0.77, 0.54, 0.50, and 0.48 for cancer stages 1, 2, 3, and 4, respectively), he noted.

The findings are noteworthy because while prior studies from other countries have shown similar rates of missed interval colorectal cancers, those findings weren’t necessarily generalizable to U.S. populations, and the rate in the United States has been unclear, Dr. Samadder said. The size of the current study and the use of statewide data reflect clinical practice and make the findings generalizable to the U.S. population and routine GI clinical practice, he noted.

Although colonoscopy is the preferred screening option for colorectal cancer, controversy exists about its effectiveness, particularly with respect to missed interval cancer, he said.

Several factors have been suggested as to the cause of missed interval cancers, including a low adenoma detection rate, incomplete colonoscopy, poor bowel preparation, and differences in tumor biology.

In this study, neither age nor gender was associated with missed interval versus detected cancer. Also, the cecal intubation rate was 92% in the missed interval cases, and bowel prep was rated as good or excellent in 92% of cases. All procedures were performed by a gastroenterologist.

"Thus, our study suggests that a low adenoma detection rate, incomplete colonoscopy, and poor bowel prep may not be the complete estimation of the missed interval cancer issue; tumor biology may play a greater role," Dr. Samadder said. The results are consistent with missed interval colorectal cancers developing from either microsatellite instability or the serrated pathway, he added.

"Future directions include determining molecular predictors of missed interval colorectal cancer, thus identifying patients and communities at greatest risk and needing increased surveillance," he said.

Dr. Samadder has served as a speaker and teacher for Cook.

ORLANDO – Colorectal cancers that are identified 6 months or more after a colonoscopy due to either a missed lesion or a new cancer development occur in 3.5%-6% of patients in the United States, findings from a large population-based retrospective cohort study suggest.

Characteristics of these missed or newly developed cancers, or "missed interval" cancers, suggest that tumor biology, rather than patient or physician factors, plays an important role in their development, Dr. N. Jewel Samadder said at the annual Digestive Disease Week.

Of 129,936 patients aged 50-80 years who underwent colonoscopy in Utah between Feb. 15, 1995, and Jan. 31, 2009, 2,659 were diagnosed with colorectal cancer, and 37 cases of a missed interval cancer that occurred 6-60 months after the index colonoscopy were identified. Using a 6- to 36-month window following the index colonoscopy, the rate of missed interval cancers was 3.5%; using a 6- to 60-month window, the rate was 6%, said Dr. Samadder of Huntsman Cancer Institute, Salt Lake City.

Nearly 85% of the missed cancers occurred in patients who underwent polypectomy at a prior colonoscopy, meaning only about 15% occurred in patients with a prior clean colonoscopy. Furthermore, missed interval colorectal cancers were significantly associated with a lower stage than were those detected at the index colonoscopy (advanced-stage odds ratio, 0.70), and were significantly more likely to be proximally located (OR, 2.24), he said.

Missed interval cancers also were associated with distinctly better survival than were detected cancers, both overall (hazard ratio, 0.63), and by stage (HR: 0.77, 0.54, 0.50, and 0.48 for cancer stages 1, 2, 3, and 4, respectively), he noted.

The findings are noteworthy because while prior studies from other countries have shown similar rates of missed interval colorectal cancers, those findings weren’t necessarily generalizable to U.S. populations, and the rate in the United States has been unclear, Dr. Samadder said. The size of the current study and the use of statewide data reflect clinical practice and make the findings generalizable to the U.S. population and routine GI clinical practice, he noted.

Although colonoscopy is the preferred screening option for colorectal cancer, controversy exists about its effectiveness, particularly with respect to missed interval cancer, he said.

Several factors have been suggested as to the cause of missed interval cancers, including a low adenoma detection rate, incomplete colonoscopy, poor bowel preparation, and differences in tumor biology.

In this study, neither age nor gender was associated with missed interval versus detected cancer. Also, the cecal intubation rate was 92% in the missed interval cases, and bowel prep was rated as good or excellent in 92% of cases. All procedures were performed by a gastroenterologist.

"Thus, our study suggests that a low adenoma detection rate, incomplete colonoscopy, and poor bowel prep may not be the complete estimation of the missed interval cancer issue; tumor biology may play a greater role," Dr. Samadder said. The results are consistent with missed interval colorectal cancers developing from either microsatellite instability or the serrated pathway, he added.

"Future directions include determining molecular predictors of missed interval colorectal cancer, thus identifying patients and communities at greatest risk and needing increased surveillance," he said.

Dr. Samadder has served as a speaker and teacher for Cook.