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Open Access 01-12-2024 | Colonoscopy | Research

Survival outcomes of population-wide colonoscopy screening: reanalysis of the NordICC data

Authors: Tomer Meirson, Gal Markel, Daniel A. Goldstein

Published in: BMC Gastroenterology | Issue 1/2024

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Abstract

Background

Colonoscopy as a common screening practice to prevent colorectal cancer lacks strong evidence. NordICC, the first randomized trial of colonoscopy screening, reported no clear clinical benefit for colonoscopy in the intention-to-screen population with suggested benefit in the risk of colorectal incidence and cancer-specific mortality in the per-protocol analyses. However, although the study was designed to perform survival analysis, no survival outcomes were reported since the underlying assumption for hazard ratio was not valid. We aimed to assess whether colonoscopy screening is associated with improved survival outcomes compared with usual care.

Methods

We reconstructed patient-level data from the Kaplan-Meier estimator of the primary endpoints reported in NordICC for the intention-to-screen and adjusted per-protocol populations. The restricted-mean survival time difference (RMST-D) and restricted-mean time loss ratio (RMTL-R), which are robust alternatives to the hazard ratio without specific model assumptions, were calculated for colorectal cancer incidence and death.

Results

In this study, no significant difference in colorectal cancer incidence over 10 years was found in the intention-to-screen population (RMST-D: -0.68 days, 95% CI -3.9–2.6; RMTL-R: 1.04, 95% CI 0.88–1.22) or in the per-protocol analysis population (RMST-D: -2.9 days, 95% CI -6.5–0.67; RMTL-R: 1.15, 95% CI 0.97–1.35). In the intention-to-screen population, inviting individuals to colonoscopy did not improve colorectal-cancer death (RMST-D: -0.29 days, 95% CI -1.6–1.0; RMTL-R: 1.07, 95% CI 0.78–1.48). Over 10 years, in the per-protocol analysis, individuals who underwent colonoscopy survived an average of 1.1 more days free of colorectal cancer, but this difference was not statistically significant (RMST-D: 95% CI -0.13–2.3; RMTL-R: 0.72, 95% CI 0.49–1.07).

Conclusions

In this reanalysis of the NordICC data, no evidence of improvement in survival outcomes for participants invited to undergo colonoscopy compared to usual care was identified, even when assuming that all invited participants did undergo colonoscopy. Thus, our results do not support the use of colonoscopy as a population-wide screening test as a mean to decrease colorectal cancer incidence or death.

Registry

Not applicable.
Literature
1.
go back to reference Helsingen LM, Kalager M. Colorectal cancer screening—approach, evidence, and future directions. NEJM Evid. 2022;1(1):EVIDra2100035.CrossRefPubMed Helsingen LM, Kalager M. Colorectal cancer screening—approach, evidence, and future directions. NEJM Evid. 2022;1(1):EVIDra2100035.CrossRefPubMed
2.
go back to reference Bretthauer M, Løberg M, Wieszczy P, Kalager M, Emilsson L, Garborg K, Rupinski M, Dekker E, Spaander M, Bugajski M. Effect of colonoscopy screening on risks of colorectal cancer and related death. N Engl J Med. 2022;387(17):1547–56.CrossRefPubMed Bretthauer M, Løberg M, Wieszczy P, Kalager M, Emilsson L, Garborg K, Rupinski M, Dekker E, Spaander M, Bugajski M. Effect of colonoscopy screening on risks of colorectal cancer and related death. N Engl J Med. 2022;387(17):1547–56.CrossRefPubMed
3.
go back to reference Ben-Aharon O, Magnezi R, Leshno M, Goldstein DA. Median survival or mean survival: which measure is the most appropriate for patients, physicians, and policymakers? Oncologist. 2019;24(11):1469–78.CrossRefPubMedPubMedCentral Ben-Aharon O, Magnezi R, Leshno M, Goldstein DA. Median survival or mean survival: which measure is the most appropriate for patients, physicians, and policymakers? Oncologist. 2019;24(11):1469–78.CrossRefPubMedPubMedCentral
4.
go back to reference Royston P, Parmar MK. The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt. Stat Med. 2011;30(19):2409–21.CrossRefPubMed Royston P, Parmar MK. The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt. Stat Med. 2011;30(19):2409–21.CrossRefPubMed
5.
go back to reference Zucker DM. Restricted mean life with covariates: modification and extension of a useful survival analysis method. J Am Stat Assoc. 1998;93(442):702–9.CrossRef Zucker DM. Restricted mean life with covariates: modification and extension of a useful survival analysis method. J Am Stat Assoc. 1998;93(442):702–9.CrossRef
6.
go back to reference Uno H, Wittes J, Fu H, Solomon SD, Claggett B, Tian L, Cai T, Pfeffer MA, Evans SR, Wei L-J. Alternatives to hazard ratios for comparing the efficacy or safety of therapies in noninferiority studies. Ann Intern Med. 2015;163(2):127–34.CrossRefPubMedPubMedCentral Uno H, Wittes J, Fu H, Solomon SD, Claggett B, Tian L, Cai T, Pfeffer MA, Evans SR, Wei L-J. Alternatives to hazard ratios for comparing the efficacy or safety of therapies in noninferiority studies. Ann Intern Med. 2015;163(2):127–34.CrossRefPubMedPubMedCentral
7.
go back to reference Uno H, Claggett B, Tian L, Inoue E, Gallo P, Miyata T, Schrag D, Takeuchi M, Uyama Y, Zhao L. Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis. J Clin Oncol. 2014;32(22):2380.CrossRefPubMedPubMedCentral Uno H, Claggett B, Tian L, Inoue E, Gallo P, Miyata T, Schrag D, Takeuchi M, Uyama Y, Zhao L. Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis. J Clin Oncol. 2014;32(22):2380.CrossRefPubMedPubMedCentral
8.
go back to reference Liang F, Zhang S, Wang Q, Li W. Treatment effects measured by restricted mean survival time in trials of immune checkpoint inhibitors for cancer. Ann Oncol. 2018;29(5):1320–4.CrossRefPubMed Liang F, Zhang S, Wang Q, Li W. Treatment effects measured by restricted mean survival time in trials of immune checkpoint inhibitors for cancer. Ann Oncol. 2018;29(5):1320–4.CrossRefPubMed
10.
go back to reference Gilboa S, Pras Y, Mataraso A, Bomze D, Markel G, Meirson T. Informative censoring of surrogate end-point data in phase 3 oncology trials. Eur J Cancer. 2021;153:190–202.CrossRefPubMed Gilboa S, Pras Y, Mataraso A, Bomze D, Markel G, Meirson T. Informative censoring of surrogate end-point data in phase 3 oncology trials. Eur J Cancer. 2021;153:190–202.CrossRefPubMed
11.
go back to reference Meirson T, Pentimalli F, Cerza F, Baglio G, Gray SG, Correale P, Krstic-Demonacos M, Markel G, Giordano A, Bomze D. Comparison of 3 randomized clinical trials of frontline therapies for malignant pleural mesothelioma. JAMA Netw Open. 2022;5(3):e221490–221490.CrossRefPubMedPubMedCentral Meirson T, Pentimalli F, Cerza F, Baglio G, Gray SG, Correale P, Krstic-Demonacos M, Markel G, Giordano A, Bomze D. Comparison of 3 randomized clinical trials of frontline therapies for malignant pleural mesothelioma. JAMA Netw Open. 2022;5(3):e221490–221490.CrossRefPubMedPubMedCentral
12.
go back to reference Holme Ø, Schoen RE, Senore C, Segnan N, Hoff G, Løberg M, Bretthauer M, Adami H-O, Kalager M. Effectiveness of flexible sigmoidoscopy screening in men and women and different age groups: pooled analysis of randomised trials. BMJ 2017, 356(8088). Holme Ø, Schoen RE, Senore C, Segnan N, Hoff G, Løberg M, Bretthauer M, Adami H-O, Kalager M. Effectiveness of flexible sigmoidoscopy screening in men and women and different age groups: pooled analysis of randomised trials. BMJ 2017, 356(8088).
13.
go back to reference Ioannidis JP. The importance of predefined rules and prespecified statistical analyses: do not abandon significance. JAMA. 2019;321(21):2067–8.CrossRefPubMed Ioannidis JP. The importance of predefined rules and prespecified statistical analyses: do not abandon significance. JAMA. 2019;321(21):2067–8.CrossRefPubMed
14.
go back to reference Hasegawa T, Uno H, Wei L-J. Neratinib after trastuzumab in patients with HER2-positive breast cancer. Lancet Oncol. 2016;17(5):e176.CrossRefPubMed Hasegawa T, Uno H, Wei L-J. Neratinib after trastuzumab in patients with HER2-positive breast cancer. Lancet Oncol. 2016;17(5):e176.CrossRefPubMed
15.
go back to reference Zhang Y, Zhang X-B, Ding Y-W, Kong Y, Zhu X-F, Li P-H, Tian Y, Zhang Q-W. Distinct time trends in colorectal cancer incidence in countries with SDI levels from 1990 to 2019: an age–period–cohort analysis for the global burden of Disease 2019 study. Front Public Health. 2024;12:1370282.CrossRefPubMedPubMedCentral Zhang Y, Zhang X-B, Ding Y-W, Kong Y, Zhu X-F, Li P-H, Tian Y, Zhang Q-W. Distinct time trends in colorectal cancer incidence in countries with SDI levels from 1990 to 2019: an age–period–cohort analysis for the global burden of Disease 2019 study. Front Public Health. 2024;12:1370282.CrossRefPubMedPubMedCentral
16.
go back to reference Araghi M, Soerjomataram I, Bardot A, Ferlay J, Cabasag CJ, Morrison DS, De P, Tervonen H, Walsh PM, Bucher O. Changes in colorectal cancer incidence in seven high-income countries: a population-based study. Lancet Gastroenterol Hepatol. 2019;4(7):511–8.CrossRefPubMed Araghi M, Soerjomataram I, Bardot A, Ferlay J, Cabasag CJ, Morrison DS, De P, Tervonen H, Walsh PM, Bucher O. Changes in colorectal cancer incidence in seven high-income countries: a population-based study. Lancet Gastroenterol Hepatol. 2019;4(7):511–8.CrossRefPubMed
17.
go back to reference Fadlallah H, El Masri J, Fakhereddine H, Youssef J, Chemaly C, Doughan S, Abou-Kheir W. Colorectal cancer: recent advances in management and treatment. World J Clin Oncol. 2024;15(9):1136.CrossRefPubMedPubMedCentral Fadlallah H, El Masri J, Fakhereddine H, Youssef J, Chemaly C, Doughan S, Abou-Kheir W. Colorectal cancer: recent advances in management and treatment. World J Clin Oncol. 2024;15(9):1136.CrossRefPubMedPubMedCentral
18.
go back to reference Desai A, Prasad V. Low-dose computed tomographic screening for lung cancer: time to implement or unresolved questions? J Gen Intern Med. 2021;36(10):3202–4.CrossRefPubMedPubMedCentral Desai A, Prasad V. Low-dose computed tomographic screening for lung cancer: time to implement or unresolved questions? J Gen Intern Med. 2021;36(10):3202–4.CrossRefPubMedPubMedCentral
19.
go back to reference Wallis M. How do we manage overdiagnosis/overtreatment in breast screening? Clin Radiol. 2018;73(4):372–80.CrossRefPubMed Wallis M. How do we manage overdiagnosis/overtreatment in breast screening? Clin Radiol. 2018;73(4):372–80.CrossRefPubMed
20.
go back to reference Prasad V. Is prostate cancer screening responsible for the negative results of prostate cancer treatment trials? Med Hypotheses. 2016;93:71–3.CrossRefPubMed Prasad V. Is prostate cancer screening responsible for the negative results of prostate cancer treatment trials? Med Hypotheses. 2016;93:71–3.CrossRefPubMed
21.
go back to reference Lui RN, Wong SH, Ding NS, Sekiguchi M, Yu J, Ang TL, Yeoh KG, Chiu HM, Sung JJ. Is this the end of colonoscopy screening for colorectal cancer? An Asia-Pacific perspective. J Gastroenterol Hepatol 2023, 38(5). Lui RN, Wong SH, Ding NS, Sekiguchi M, Yu J, Ang TL, Yeoh KG, Chiu HM, Sung JJ. Is this the end of colonoscopy screening for colorectal cancer? An Asia-Pacific perspective. J Gastroenterol Hepatol 2023, 38(5).
22.
go back to reference Kastrinos F, Kupfer SS, Gupta S. Colorectal cancer risk assessment and precision approaches to screening: brave new world or worlds apart? Gastroenterol 2023, 164(5):812–27. Kastrinos F, Kupfer SS, Gupta S. Colorectal cancer risk assessment and precision approaches to screening: brave new world or worlds apart? Gastroenterol 2023, 164(5):812–27.
23.
go back to reference Plys E, Bulliard J-L, Chaouch A, Durand M-A, van Duuren LA, Brändle K, Auer R, Froehlich F, Lansdorp-Vogelaar I, Corley DA. Colorectal cancer screening decision based on predicted risk: protocol for a pilot randomized controlled trial. JMIR Res Protoc. 2023;12(1):e46865.CrossRefPubMedPubMedCentral Plys E, Bulliard J-L, Chaouch A, Durand M-A, van Duuren LA, Brändle K, Auer R, Froehlich F, Lansdorp-Vogelaar I, Corley DA. Colorectal cancer screening decision based on predicted risk: protocol for a pilot randomized controlled trial. JMIR Res Protoc. 2023;12(1):e46865.CrossRefPubMedPubMedCentral
24.
go back to reference Chen H, Shi J, Lu M, Li Y, Du L, Liao X, Wei D, Dong D, Gao Y, Zhu C. Comparison of colonoscopy, fecal immunochemical test, and risk-adapted approach in a colorectal cancer screening trial (TARGET-C). Clin Gastroenterol Hepatol. 2023;21(3):808–18.CrossRefPubMed Chen H, Shi J, Lu M, Li Y, Du L, Liao X, Wei D, Dong D, Gao Y, Zhu C. Comparison of colonoscopy, fecal immunochemical test, and risk-adapted approach in a colorectal cancer screening trial (TARGET-C). Clin Gastroenterol Hepatol. 2023;21(3):808–18.CrossRefPubMed
25.
go back to reference Meirson T, Neiman V, Sternschuss M, Markel G, Tannock IF. Clarification needed for pembrolizumab as adjuvant therapy in clear cell renal cell carcinoma. Lancet Oncol. 2022;23(11):e489.CrossRefPubMed Meirson T, Neiman V, Sternschuss M, Markel G, Tannock IF. Clarification needed for pembrolizumab as adjuvant therapy in clear cell renal cell carcinoma. Lancet Oncol. 2022;23(11):e489.CrossRefPubMed
26.
go back to reference Horesh N, Bomze D, Lim C, Markel G, Meirson T, Azoulay D. Systemic review of the robustness of randomized controlled trials for the treatment of cholangiocarcinoma in three domains: survival-inferred fragility index, restricted mean survival time, and the spin effect. Hepatobiliary Surg Nutr. 2022;11(6):861–9.CrossRefPubMedPubMedCentral Horesh N, Bomze D, Lim C, Markel G, Meirson T, Azoulay D. Systemic review of the robustness of randomized controlled trials for the treatment of cholangiocarcinoma in three domains: survival-inferred fragility index, restricted mean survival time, and the spin effect. Hepatobiliary Surg Nutr. 2022;11(6):861–9.CrossRefPubMedPubMedCentral
27.
go back to reference Gilboa S, Bomze D, Markel G, Meirson T. Radiographic progression-free survival in the ACIS trial for prostate cancer. Lancet Oncol. 2022;23(1):e3.CrossRefPubMed Gilboa S, Bomze D, Markel G, Meirson T. Radiographic progression-free survival in the ACIS trial for prostate cancer. Lancet Oncol. 2022;23(1):e3.CrossRefPubMed
28.
go back to reference Bomze D, Asher N, Ali OH, Flatz L, Azoulay D, Markel G, Meirson T. Survival-inferred fragility index of phase 3 clinical trials evaluating immune checkpoint inhibitors. JAMA Netw Open. 2020;3(10):e2017675–2017675.CrossRefPubMedPubMedCentral Bomze D, Asher N, Ali OH, Flatz L, Azoulay D, Markel G, Meirson T. Survival-inferred fragility index of phase 3 clinical trials evaluating immune checkpoint inhibitors. JAMA Netw Open. 2020;3(10):e2017675–2017675.CrossRefPubMedPubMedCentral
Metadata
Title
Survival outcomes of population-wide colonoscopy screening: reanalysis of the NordICC data
Authors
Tomer Meirson
Gal Markel
Daniel A. Goldstein
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2024
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-024-03506-2

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