Screening yields long-term reduction in CRC mortality

SAN DIEGO – The mortality-reducing benefit of colorectal cancer screening persists long term, according to an updated analysis of the randomized Minnesota Fecal Occult Blood Trial.

Investigators led by Dr. Aasma Shaukat, a gastroenterologist with the University of Minnesota, Minneapolis, analyzed data for more than 46,000 participants aged 50-80 years who were assigned to screening with the fecal occult blood test (FOBT) or no screening.

After the first 18 years, the cumulative colorectal cancer mortality rate was reduced by one-third with annual screening and by one-fifth with biennial screening as compared with no screening, according to initially reported results (J. Natl. Cancer Inst. 1999;91:434-7).

The updated results, now after 30 years of follow-up – the longest of any such trial to date – showed that the reductions in risk with screening were essentially unchanged, Dr. Shaukat reported at the annual meeting of the American College of Gastroenterology.

"Screening for colon cancer using fecal occult blood testing consistently reduces colorectal cancer mortality..., and this effect is sustained through 30 years of follow-up," she commented. "This suggests the effect of polypectomy, because [if] fecal occult blood testing [detected only] early cancers, most of the benefit would be seen in the first 8-10 years. The sustained benefit suggests that these individuals underwent removal of polyps that would have turned into cancer and resulted in a death at 30 years."

In additional trial findings, the benefit of screening appeared to be greater for men than women and greater for those who began screening after the age of 60 years.

Session attendee Dr. Samir Gupta, of the University of California, San Diego, asked, "After the initial 10 or 15 years of protocolized screening, is it possible that screening was going on in the control group" and that might explain the lesser benefit in younger individuals, as they would have had more time to be screened.

"During the trial, through 1998, the screening in the control group was less than 5%, so there wasn’t much screening going on in the control group," Dr. Shaukat replied. However, "after the trial ended, we don’t have information on people’s screening behavior. And screening became popular, particularly in the last two decades. So there is a possibility that a large number of people that were in the control group underwent screening, and that’s diluting the effects that we would have otherwise seen."

She offered a few possible additional reasons for the smaller benefit in the younger group. "One is that group doesn’t have a higher risk of colon cancer and of dying from colon cancer, and hence, we are just not seeing the effect of screening," she said. "The second is that perhaps fecal occult blood testing is fairly insensitive in that age group; that’s something that needs to be explored further."

Session comoderator Dr. Jonathan A. Leighton of the Mayo Clinic in Scottsdale, Ariz., asked, "Why do you think there was that benefit in men over women?"

"That’s something that’s actually been shown in several natural history and modeling studies," Dr. Shaukat replied. "Men have a higher incidence of colon cancer and they have a higher risk of dying from colon cancer compared to women. So it bears to reason that we would see a larger effect of screening among men compared to women." That said, subgroup analyses should be considered hypothesis generating and require confirmation, she acknowledged.

Dr. Carol Burke of the Cleveland Clinic, who also attended the session, asked whether the screening benefit would have been even greater in analyses restricted to adherent patients.

"Compliance-adjusted estimates ... are a lot larger, to the magnitude of about a 40% reduction in colorectal cancer mortality," Dr. Shaukat replied.

"What effect do you think FIT [fecal immunochemical test] would have on the magnitude [of benefit] – similar for FIT or better because of adherence?" Dr. Burke further queried.

"These fecal occult blood tests were rehydrated, so their sensitivity is comparable to modern-day FIT. So we expect FIT to do the same if not better," Dr. Shaukat replied.

In the trial, 46,551 participants in the Minnesota Colon Cancer Control Study were assigned to annual or biennial screening or no screening between 1976 and 1992. Those with positive FOBT results underwent colonoscopy with polypectomy if needed. All groups had annual follow-up thereafter through 1998.

Adherence to screening was high in the trial, with 90% of participants in the screening groups completing at least one FOBT, and no difference between men and women, according to Dr. Shaukat.

At each screening, 10% of participants had positive results, and 83% of this subset overall underwent colonoscopy. The complication rate from colonoscopy was low, at less than 0.1%.

In the updated analysis, 71% of trial participants had died as ascertained from the National Death Index.

In intention-to-treat analyses, the risk of colorectal cancer mortality was a significant 32% lower in the group screened annually (relative risk, 0.68) and 22% lower in the group screened biennially (RR, 0.78) as compared with the nonscreened group, according to data reported at the meeting and recently published (N. Engl. J. Med. 2013;369:1106-14).

"We don’t know what happened after 1998," Dr. Shaukat reminded attendees. "At best, the effects that we are seeing might be dilute, and if truly the control group had remained unscreened, we would have seen perhaps larger differences."

The absolute cumulative colorectal cancer mortality rates were 0.02 with annual screening, 0.02 with biennial screening, and 0.03 with no screening. "This separation [in curves] started at about 13 years of follow-up and persisted through 30 years of follow-up," she pointed out.

All-cause mortality was statistically indistinguishable between groups, although the trial was underpowered to assess this outcome.

In subgroup analyses, there was a near-significant interaction of screening with sex (P = .06), whereby the benefit was greater among men (RR, 0.62) than among women (RR, 0.83).

Additionally, among men, there was a significant interaction with age (P = .04), whereby screening was most beneficial among those 60-69 years old at baseline (RR, 0.46). The benefit among women appeared to be restricted to those who started screening at age 60 or later.

"We don’t have information on the incidence of colon cancer, and hence we can’t comment on right- versus left-sided colon cancer mortality," Dr. Shaukat noted.

Dr. Shaukat disclosed no conflicts of interest.

SAN DIEGO – The mortality-reducing benefit of colorectal cancer screening persists long term, according to an updated analysis of the randomized Minnesota Fecal Occult Blood Trial.

Investigators led by Dr. Aasma Shaukat, a gastroenterologist with the University of Minnesota, Minneapolis, analyzed data for more than 46,000 participants aged 50-80 years who were assigned to screening with the fecal occult blood test (FOBT) or no screening.

After the first 18 years, the cumulative colorectal cancer mortality rate was reduced by one-third with annual screening and by one-fifth with biennial screening as compared with no screening, according to initially reported results (J. Natl. Cancer Inst. 1999;91:434-7).

The updated results, now after 30 years of follow-up – the longest of any such trial to date – showed that the reductions in risk with screening were essentially unchanged, Dr. Shaukat reported at the annual meeting of the American College of Gastroenterology.

"Screening for colon cancer using fecal occult blood testing consistently reduces colorectal cancer mortality..., and this effect is sustained through 30 years of follow-up," she commented. "This suggests the effect of polypectomy, because [if] fecal occult blood testing [detected only] early cancers, most of the benefit would be seen in the first 8-10 years. The sustained benefit suggests that these individuals underwent removal of polyps that would have turned into cancer and resulted in a death at 30 years."

In additional trial findings, the benefit of screening appeared to be greater for men than women and greater for those who began screening after the age of 60 years.

Session attendee Dr. Samir Gupta, of the University of California, San Diego, asked, "After the initial 10 or 15 years of protocolized screening, is it possible that screening was going on in the control group" and that might explain the lesser benefit in younger individuals, as they would have had more time to be screened.

"During the trial, through 1998, the screening in the control group was less than 5%, so there wasn’t much screening going on in the control group," Dr. Shaukat replied. However, "after the trial ended, we don’t have information on people’s screening behavior. And screening became popular, particularly in the last two decades. So there is a possibility that a large number of people that were in the control group underwent screening, and that’s diluting the effects that we would have otherwise seen."

She offered a few possible additional reasons for the smaller benefit in the younger group. "One is that group doesn’t have a higher risk of colon cancer and of dying from colon cancer, and hence, we are just not seeing the effect of screening," she said. "The second is that perhaps fecal occult blood testing is fairly insensitive in that age group; that’s something that needs to be explored further."

Session comoderator Dr. Jonathan A. Leighton of the Mayo Clinic in Scottsdale, Ariz., asked, "Why do you think there was that benefit in men over women?"

"That’s something that’s actually been shown in several natural history and modeling studies," Dr. Shaukat replied. "Men have a higher incidence of colon cancer and they have a higher risk of dying from colon cancer compared to women. So it bears to reason that we would see a larger effect of screening among men compared to women." That said, subgroup analyses should be considered hypothesis generating and require confirmation, she acknowledged.

Dr. Carol Burke of the Cleveland Clinic, who also attended the session, asked whether the screening benefit would have been even greater in analyses restricted to adherent patients.

"Compliance-adjusted estimates ... are a lot larger, to the magnitude of about a 40% reduction in colorectal cancer mortality," Dr. Shaukat replied.

"What effect do you think FIT [fecal immunochemical test] would have on the magnitude [of benefit] – similar for FIT or better because of adherence?" Dr. Burke further queried.

"These fecal occult blood tests were rehydrated, so their sensitivity is comparable to modern-day FIT. So we expect FIT to do the same if not better," Dr. Shaukat replied.

In the trial, 46,551 participants in the Minnesota Colon Cancer Control Study were assigned to annual or biennial screening or no screening between 1976 and 1992. Those with positive FOBT results underwent colonoscopy with polypectomy if needed. All groups had annual follow-up thereafter through 1998.

Adherence to screening was high in the trial, with 90% of participants in the screening groups completing at least one FOBT, and no difference between men and women, according to Dr. Shaukat.

At each screening, 10% of participants had positive results, and 83% of this subset overall underwent colonoscopy. The complication rate from colonoscopy was low, at less than 0.1%.

In the updated analysis, 71% of trial participants had died as ascertained from the National Death Index.

In intention-to-treat analyses, the risk of colorectal cancer mortality was a significant 32% lower in the group screened annually (relative risk, 0.68) and 22% lower in the group screened biennially (RR, 0.78) as compared with the nonscreened group, according to data reported at the meeting and recently published (N. Engl. J. Med. 2013;369:1106-14).

"We don’t know what happened after 1998," Dr. Shaukat reminded attendees. "At best, the effects that we are seeing might be dilute, and if truly the control group had remained unscreened, we would have seen perhaps larger differences."

The absolute cumulative colorectal cancer mortality rates were 0.02 with annual screening, 0.02 with biennial screening, and 0.03 with no screening. "This separation [in curves] started at about 13 years of follow-up and persisted through 30 years of follow-up," she pointed out.

All-cause mortality was statistically indistinguishable between groups, although the trial was underpowered to assess this outcome.

In subgroup analyses, there was a near-significant interaction of screening with sex (P = .06), whereby the benefit was greater among men (RR, 0.62) than among women (RR, 0.83).

Additionally, among men, there was a significant interaction with age (P = .04), whereby screening was most beneficial among those 60-69 years old at baseline (RR, 0.46). The benefit among women appeared to be restricted to those who started screening at age 60 or later.

"We don’t have information on the incidence of colon cancer, and hence we can’t comment on right- versus left-sided colon cancer mortality," Dr. Shaukat noted.

Dr. Shaukat disclosed no conflicts of interest.

SAN DIEGO – The mortality-reducing benefit of colorectal cancer screening persists long term, according to an updated analysis of the randomized Minnesota Fecal Occult Blood Trial.

Investigators led by Dr. Aasma Shaukat, a gastroenterologist with the University of Minnesota, Minneapolis, analyzed data for more than 46,000 participants aged 50-80 years who were assigned to screening with the fecal occult blood test (FOBT) or no screening.

After the first 18 years, the cumulative colorectal cancer mortality rate was reduced by one-third with annual screening and by one-fifth with biennial screening as compared with no screening, according to initially reported results (J. Natl. Cancer Inst. 1999;91:434-7).

The updated results, now after 30 years of follow-up – the longest of any such trial to date – showed that the reductions in risk with screening were essentially unchanged, Dr. Shaukat reported at the annual meeting of the American College of Gastroenterology.

"Screening for colon cancer using fecal occult blood testing consistently reduces colorectal cancer mortality..., and this effect is sustained through 30 years of follow-up," she commented. "This suggests the effect of polypectomy, because [if] fecal occult blood testing [detected only] early cancers, most of the benefit would be seen in the first 8-10 years. The sustained benefit suggests that these individuals underwent removal of polyps that would have turned into cancer and resulted in a death at 30 years."

In additional trial findings, the benefit of screening appeared to be greater for men than women and greater for those who began screening after the age of 60 years.

Session attendee Dr. Samir Gupta, of the University of California, San Diego, asked, "After the initial 10 or 15 years of protocolized screening, is it possible that screening was going on in the control group" and that might explain the lesser benefit in younger individuals, as they would have had more time to be screened.

"During the trial, through 1998, the screening in the control group was less than 5%, so there wasn’t much screening going on in the control group," Dr. Shaukat replied. However, "after the trial ended, we don’t have information on people’s screening behavior. And screening became popular, particularly in the last two decades. So there is a possibility that a large number of people that were in the control group underwent screening, and that’s diluting the effects that we would have otherwise seen."

She offered a few possible additional reasons for the smaller benefit in the younger group. "One is that group doesn’t have a higher risk of colon cancer and of dying from colon cancer, and hence, we are just not seeing the effect of screening," she said. "The second is that perhaps fecal occult blood testing is fairly insensitive in that age group; that’s something that needs to be explored further."

Session comoderator Dr. Jonathan A. Leighton of the Mayo Clinic in Scottsdale, Ariz., asked, "Why do you think there was that benefit in men over women?"

"That’s something that’s actually been shown in several natural history and modeling studies," Dr. Shaukat replied. "Men have a higher incidence of colon cancer and they have a higher risk of dying from colon cancer compared to women. So it bears to reason that we would see a larger effect of screening among men compared to women." That said, subgroup analyses should be considered hypothesis generating and require confirmation, she acknowledged.

Dr. Carol Burke of the Cleveland Clinic, who also attended the session, asked whether the screening benefit would have been even greater in analyses restricted to adherent patients.

"Compliance-adjusted estimates ... are a lot larger, to the magnitude of about a 40% reduction in colorectal cancer mortality," Dr. Shaukat replied.

"What effect do you think FIT [fecal immunochemical test] would have on the magnitude [of benefit] – similar for FIT or better because of adherence?" Dr. Burke further queried.

"These fecal occult blood tests were rehydrated, so their sensitivity is comparable to modern-day FIT. So we expect FIT to do the same if not better," Dr. Shaukat replied.

In the trial, 46,551 participants in the Minnesota Colon Cancer Control Study were assigned to annual or biennial screening or no screening between 1976 and 1992. Those with positive FOBT results underwent colonoscopy with polypectomy if needed. All groups had annual follow-up thereafter through 1998.

Adherence to screening was high in the trial, with 90% of participants in the screening groups completing at least one FOBT, and no difference between men and women, according to Dr. Shaukat.

At each screening, 10% of participants had positive results, and 83% of this subset overall underwent colonoscopy. The complication rate from colonoscopy was low, at less than 0.1%.

In the updated analysis, 71% of trial participants had died as ascertained from the National Death Index.

In intention-to-treat analyses, the risk of colorectal cancer mortality was a significant 32% lower in the group screened annually (relative risk, 0.68) and 22% lower in the group screened biennially (RR, 0.78) as compared with the nonscreened group, according to data reported at the meeting and recently published (N. Engl. J. Med. 2013;369:1106-14).

"We don’t know what happened after 1998," Dr. Shaukat reminded attendees. "At best, the effects that we are seeing might be dilute, and if truly the control group had remained unscreened, we would have seen perhaps larger differences."

The absolute cumulative colorectal cancer mortality rates were 0.02 with annual screening, 0.02 with biennial screening, and 0.03 with no screening. "This separation [in curves] started at about 13 years of follow-up and persisted through 30 years of follow-up," she pointed out.

All-cause mortality was statistically indistinguishable between groups, although the trial was underpowered to assess this outcome.

In subgroup analyses, there was a near-significant interaction of screening with sex (P = .06), whereby the benefit was greater among men (RR, 0.62) than among women (RR, 0.83).

Additionally, among men, there was a significant interaction with age (P = .04), whereby screening was most beneficial among those 60-69 years old at baseline (RR, 0.46). The benefit among women appeared to be restricted to those who started screening at age 60 or later.

"We don’t have information on the incidence of colon cancer, and hence we can’t comment on right- versus left-sided colon cancer mortality," Dr. Shaukat noted.

Dr. Shaukat disclosed no conflicts of interest.