Therapeutics
Invitation for flexible sigmoidoscopy screening reduced colorectal cancer and colorectal cancer mortality
Holme Ø, Løberg M, Kalager M, et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA. 2014;312:606-15.
Clinical impact ratings: F ★★★★★✩✩ g ★★★★★★✩ G ★★★★★★✩ Question
Commentary
Does an invitation for flexible sigmoidoscopy screening reduce colorectal cancer (CRC) incidence and mortality?
The intervention in NORCCAP was sigmoidoscopy alone or with an FOBT, but because no additional cancers or adenomas were detected with addition of a single FOBT, the intervention could be considered mainly sigmoidoscopy. The trial has particular strengths: Participants were sampled from the population, and the control group received virtually no screening.
Methods Design: Population-based, randomized, controlled trial (RCT) (Norwegian Colorectal Cancer Prevention Trial [NORCCAP]). ClinicalTrials.gov NCT00119912. Allocation: Concealed.* Blinding: Unblinded.* Follow-up period: Median 11 years. Setting: Norway. Patients: 100 210 adults 55 to 64 years of age (mean age 56 y, 50% women) who lived in 1 of 2 specified areas of Norway and were part of the Norwegian Population Register. Exclusion criteria included CRC. Intervention: Invitation by mail for screening with once-only flexible sigmoidoscopy alone (n = 10 392) or with an immunologic fecal occult blood test (FOBT) (n = 10 388), or no contact (n = 79 430). Screening examinations were done at 3 clinical centers. Outcomes: CRC incidence and CRC mortality. Secondary outcomes included all-cause mortality. Patient follow-up: 99% (intention-to-treat analysis).
Main results Screening rates in the invitation to FS only and FS plus FOBT groups were 65% and 61% (P < 0.001). The overall invitation group had lower risk for CRC incidence and CRC mortality, but not overall mortality, than did the no-contact group (Table).
Conclusion An invitation for flexible sigmoidoscopy screening reduced colorectal cancer incidence and mortality, but not all-cause mortality, compared with no contact. *See Glossary.
Sources of funding: Norwegian Cancer Society; Research Council of Norway; South-East Regional Health Authority of Norway; Fulbright Foundation; Sorlandet Hospital Kristiansand; National Institutes of Health. For correspondence: Dr. Ø. Holme, Sorlandet Hospital Kristiansand, Kristiansand, Norway. E-mail [email protected]. ■ Invitation for screening with flexible sigmoidoscopy, with or without FOBT, vs no contact† Outcomes
Cases/100 000 At a median 11 y person-y Invitation No RRR (95% CI) NNT (CI) contact
Colorectal cancer incidence
113
141
20% (8 to 30) 362 (241 to 906)
Colorectal cancer mortality
31
43
27% (6 to 44) 884 (542 to 3977)
969
995
All-cause mortality
3% (−2 to 7)
Not significant
†FOBT = fecal occult blood test; other abbreviations defined in Glossary. RRR, NNT, and CI calculated from hazard ratios and control event rates in article.
JC2
© 2014 American College of Physicians
NORCCAP is 1 of 4 large RCTs (1-3) comparing screening sigmoidoscopy with usual care. The 4 trials reported remarkably similar reductions in both CRC incidence (18% to 23%) and CRC mortality (22% to 31%). Such agreement is unusual, even among well-conducted trials, particularly given the substantial differences across the trials in CRC prevalence, willingness to be screened, threshold for follow-up colonoscopy, and unplanned screening among controls. The effects of screening seemed to be robust enough not to be strongly affected by these differences. The primary intention-to-treat analyses approximate a real-world situation in which many participants, in this case 37%, do not have the offered examinations. The authors estimate that if everyone who was offered screening had accepted, reductions in CRC incidence and mortality would have been twice as high. All-cause mortality was not reduced by screening, but this does not necessarily mean that deaths caused by screening offset the CRC deaths prevented. No procedure-related deaths occurred in the screened group, and CRC deaths comprised such a small proportion of all deaths (4%) that even a study of this size could not be expected to detect a difference in mortality rates if it existed. Despite mounting evidence of the effectiveness of sigmoidoscopy screening, its use in the USA has declined to < 1% of screened adults (4). Screening in the USA mainly relies on colonoscopy, perhaps because examination of only the left colon seems incomplete, akin to screening just 1 breast. Actually, sigmoidoscopy reduced rates of proximal colorectal cancer by 10% and CRC deaths even more, probably because distal findings prompted colonoscopic examination of the entire colon. Even if sigmoidoscopy is not a preferred screening test, these trials provide the best current evidence (albeit indirect) that screening colonoscopy is effective, at least for the left colon. Robert Fletcher, MD, MSc Harvard Medical School Boston, Massachusetts, USA References 1. Atkin WS, Edwards R, Kralj-Hnas I, et al; UK Flexible Sigmoidoscopy Trial Investigators. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicenter randomized controlled trial. Lancet. 2010;375:1624-33. 2. Segnan N, Armaroli P, Bonelli L, et al; SCORE Working Group. Onceonly sigmoidoscopy in colorectal cancer screening: Follow-up findings of the Italian randomized controlled trial—SCORE. J Nat Cancer Inst. 2011;103:1310-22. 3. Schoen RE, Pnisky PF, Weissfeld JL, et al; PLCO Project Team. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012;366:2345-57. 4. Centers for Disease Control and Prevention (CDC). Vital signs: colorectal cancer screening test use—United States, 2012. MMWR Morb Mortal Wkly Rep. 2013;62:881-8.
16 December 2014 | ACP Journal Club | Volume 161 • Number 12
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/931809/ by a University of California San Diego User on 03/30/2017
Invitation for flexible sigmoidoscopy screening reduced colorectal cancer and colorectal cancer mortality
Holme Ø, Løberg M, Kalager M, et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA. 2014;312:606-15.
Clinical impact ratings: F ★★★★★✩✩ g ★★★★★★✩ G ★★★★★★✩ Question
Commentary
Does an invitation for flexible sigmoidoscopy screening reduce colorectal cancer (CRC) incidence and mortality?
The intervention in NORCCAP was sigmoidoscopy alone or with an FOBT, but because no additional cancers or adenomas were detected with addition of a single FOBT, the intervention could be considered mainly sigmoidoscopy. The trial has particular strengths: Participants were sampled from the population, and the control group received virtually no screening.
Methods Design: Population-based, randomized, controlled trial (RCT) (Norwegian Colorectal Cancer Prevention Trial [NORCCAP]). ClinicalTrials.gov NCT00119912. Allocation: Concealed.* Blinding: Unblinded.* Follow-up period: Median 11 years. Setting: Norway. Patients: 100 210 adults 55 to 64 years of age (mean age 56 y, 50% women) who lived in 1 of 2 specified areas of Norway and were part of the Norwegian Population Register. Exclusion criteria included CRC. Intervention: Invitation by mail for screening with once-only flexible sigmoidoscopy alone (n = 10 392) or with an immunologic fecal occult blood test (FOBT) (n = 10 388), or no contact (n = 79 430). Screening examinations were done at 3 clinical centers. Outcomes: CRC incidence and CRC mortality. Secondary outcomes included all-cause mortality. Patient follow-up: 99% (intention-to-treat analysis).
Main results Screening rates in the invitation to FS only and FS plus FOBT groups were 65% and 61% (P < 0.001). The overall invitation group had lower risk for CRC incidence and CRC mortality, but not overall mortality, than did the no-contact group (Table).
Conclusion An invitation for flexible sigmoidoscopy screening reduced colorectal cancer incidence and mortality, but not all-cause mortality, compared with no contact. *See Glossary.
Sources of funding: Norwegian Cancer Society; Research Council of Norway; South-East Regional Health Authority of Norway; Fulbright Foundation; Sorlandet Hospital Kristiansand; National Institutes of Health. For correspondence: Dr. Ø. Holme, Sorlandet Hospital Kristiansand, Kristiansand, Norway. E-mail [email protected]. ■ Invitation for screening with flexible sigmoidoscopy, with or without FOBT, vs no contact† Outcomes
Cases/100 000 At a median 11 y person-y Invitation No RRR (95% CI) NNT (CI) contact
Colorectal cancer incidence
113
141
20% (8 to 30) 362 (241 to 906)
Colorectal cancer mortality
31
43
27% (6 to 44) 884 (542 to 3977)
969
995
All-cause mortality
3% (−2 to 7)
Not significant
†FOBT = fecal occult blood test; other abbreviations defined in Glossary. RRR, NNT, and CI calculated from hazard ratios and control event rates in article.
JC2
© 2014 American College of Physicians
NORCCAP is 1 of 4 large RCTs (1-3) comparing screening sigmoidoscopy with usual care. The 4 trials reported remarkably similar reductions in both CRC incidence (18% to 23%) and CRC mortality (22% to 31%). Such agreement is unusual, even among well-conducted trials, particularly given the substantial differences across the trials in CRC prevalence, willingness to be screened, threshold for follow-up colonoscopy, and unplanned screening among controls. The effects of screening seemed to be robust enough not to be strongly affected by these differences. The primary intention-to-treat analyses approximate a real-world situation in which many participants, in this case 37%, do not have the offered examinations. The authors estimate that if everyone who was offered screening had accepted, reductions in CRC incidence and mortality would have been twice as high. All-cause mortality was not reduced by screening, but this does not necessarily mean that deaths caused by screening offset the CRC deaths prevented. No procedure-related deaths occurred in the screened group, and CRC deaths comprised such a small proportion of all deaths (4%) that even a study of this size could not be expected to detect a difference in mortality rates if it existed. Despite mounting evidence of the effectiveness of sigmoidoscopy screening, its use in the USA has declined to < 1% of screened adults (4). Screening in the USA mainly relies on colonoscopy, perhaps because examination of only the left colon seems incomplete, akin to screening just 1 breast. Actually, sigmoidoscopy reduced rates of proximal colorectal cancer by 10% and CRC deaths even more, probably because distal findings prompted colonoscopic examination of the entire colon. Even if sigmoidoscopy is not a preferred screening test, these trials provide the best current evidence (albeit indirect) that screening colonoscopy is effective, at least for the left colon. Robert Fletcher, MD, MSc Harvard Medical School Boston, Massachusetts, USA References 1. Atkin WS, Edwards R, Kralj-Hnas I, et al; UK Flexible Sigmoidoscopy Trial Investigators. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicenter randomized controlled trial. Lancet. 2010;375:1624-33. 2. Segnan N, Armaroli P, Bonelli L, et al; SCORE Working Group. Onceonly sigmoidoscopy in colorectal cancer screening: Follow-up findings of the Italian randomized controlled trial—SCORE. J Nat Cancer Inst. 2011;103:1310-22. 3. Schoen RE, Pnisky PF, Weissfeld JL, et al; PLCO Project Team. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012;366:2345-57. 4. Centers for Disease Control and Prevention (CDC). Vital signs: colorectal cancer screening test use—United States, 2012. MMWR Morb Mortal Wkly Rep. 2013;62:881-8.
16 December 2014 | ACP Journal Club | Volume 161 • Number 12
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/931809/ by a University of California San Diego User on 03/30/2017
