Colonoscopy Intervals and Colorectal Cancer Incidence after Adenoma Removal

Author(s): Rodrigo Jover, M.D., Ph.D.^1,2,3; Michael Bretthauer, M.D., Ph.D.^4,5; Joaquin Cubiella, M.D., Ph.D.⁶; Sarah J.E. Barry, Ph.D.⁷; Anna Macios, Ph.D.^4,5; Lauren Barnett, Ph.D.⁷; Rune Erichsen, M.D., Ph.D.^8,9,10; Michal F. Kaminski, M.D., Ph.D.^11,12,13; Hans-Olov Adami, M.D., Ph.D.^4,5,14; Øyvind Holme, M.D., Ph.D.^4,15; Joep Ijspeert, M.D., Ph.D.¹⁶; Monika Ferlitsch, M.D.^17,18; Mario Dinis-Ribeiro, M.D., Ph.D.^19,20,21; Maria Pellise, M.D., Ph.D.²²; Alejandro Martínez-Roca, Ph.D.^1,2,3; Sandra Baile-Maxía, M.D., Ph.D.^1,2,3; Luisa de-Castro, M.D., Ph.D.²³; Luis Bujanda, M.D., Ph.D.²⁴; Pilar Díez-Redondo, M.D., Ph.D.²⁵; Jens Aksel Nordberg Nilsen, M.D.^4,5,26; Hong Dung Nguyen, M.D.²⁷; Linn Bernklev, M.D.^4,28; Jørgen Tilma, M.D.²⁹; Uffe Schou Løve, M.D.³⁰; Claudia Jaensch, M.D., Ph.D.^31,32; Nastazja D. Pilonis, M.D., Ph.D.¹¹; Mirosław Szura, M.D.³³; Andrzej Bialek, M.D.³⁴; Annemarie van Berkel, M.D., Ph.D.³⁵; Manon C.W. Spaander, M.D., Ph.D.³⁶; Frank ter Borg, M.D., Ph.D.³⁷; Monique E. van Leerdam, M.D., Ph.D.³⁸; Miguel A. Hernán, M.D., Ph.D.³⁹; Jaroslaw Regula, M.D., Ph.D.^11,12; Magnus Løberg, M.D., Ph.D.^4,5; Evelien Dekker, M.D., Ph.D.⁴⁰; Mette Kalager, M.D., Ph.D.^4,5; the EPoS Study Group*;

Source: DOI: 10.1056/NEJMoa2603816

Dr. Anjan Patel's Thoughts

This one could reshape post-polypectomy surveillance. In nearly 11,000 patients with high-risk adenomas, waiting 5 years instead of 3 for the first surveillance colonoscopy was noninferior for colorectal cancer incidence (under 1% in both arms), with no apparent shift toward later-stage disease and roughly half as many colonoscopies. The 3-year arm picked up more advanced adenomas (15% vs 11%), but that didn't translate into fewer or earlier cancers. Caveats: this is an interim analysis that only narrowly met noninferiority, and only about two-thirds of patients completed 5-year surveillance, so the 10-year data will be the real test before guidelines move.

BACKGROUND

More evidence is needed to inform recommendations for intervals of colonoscopy surveillance after polyp removal.

METHODS

In this ongoing noninferiority trial conducted in eight European countries, we randomly assigned patients with high-risk adenomas (defined as ≥1 adenoma with a diameter of ≥10 mm, high-grade dysplasia, or villous growth or 3 to 10 adenomas of any kind) to undergo a first colonoscopy 5 years after polyp removal or 3 years; surveillance 3 years is currently recommended in guidelines. The 3-year group also underwent colonoscopy 5 years. The primary end point is the cumulative incidence of colorectal cancer 10 years, with a prespecified noninferiority margin of 0.7 percentage points for the upper boundary of the confidence interval for the difference between the two groups. Here, we report the results of an interim analysis conducted after 5.5 years of follow-up. Inverse probability weighting was used to account for missing data owing to nonparticipation in surveillance colonoscopy 5 years. In this analysis, the incidence of colorectal cancer is reported with a one-sided 99.12% confidence interval; for the final analysis 10 years, the plan is to calculate a 95.33% confidence interval to maintain an overall type I error of 5%. Research Summary Colonoscopy Intervals and Colorectal Cancer after Adenoma Removal

RESULTS

A total of 10,799 patients underwent randomization: 5398 patients were assigned to the 5-year group and 5401 to the 3-year group. The 5-year cumulative incidence of colorectal cancer was 0.77% with less-frequent surveillance and 0.82% with more-frequent surveillance (difference, −0.05 percentage points); the upper boundary of the 99.12% confidence interval was 0.68, which met the criterion for noninferiority. The distribution of cancer stage diagnosis did not appear to differ substantially between the two groups. A total of 5 patients died of colorectal cancer: 3 patients (0.06%) in the 5-year group and 2 (0.04%) in the 3-year group.

CONCLUSIONS

In this interim analysis of a 10-year noninferiority trial, beginning surveillance colonoscopy 5 years after polyp removal was noninferior to beginning 3 years with respect to the cumulative incidence of colorectal cancer 5 years among patients with high-risk adenomas. (Funded by the Research Council of Norway and others; EPoS II ClinicalTrials.gov number, NCT02319928.) Quick Take Colonoscopy Intervals after Adenoma Removal 1m 59s

Author Affiliations

¹Servicio de Medicina Digestiva, Hospital General Universitario Dr. Balmis, CIBERehd, Alicante, Spain; ²Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain; ³Departamento de Medicina Clínica, Universidad Miguel Hernández, Alicante, Spain; ⁴Clinical Effectiveness Research Group, Institute of Health and Society and Institute of Clinical Medicine, University of Oslo, Oslo; ⁵Department of Transplantation Medicine, Oslo University Hospital, Oslo; ⁶Department of Gastroenterology, Hospital Universitario de Ourense, Grupo de Investigación en Oncología Digestiva-Ourense, CIBERehd, Ourense, Spain; ⁷Frontier Science Scotland, Kincraig, United Kingdom; ⁸Department of Surgery, Randers Regional Hospital, Randers, Denmark; ⁹University Clinic for Coloproctology and Endoscopy, Randers Regional Hospital, Randers, Denmark; ¹⁰Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; ¹¹Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; ¹²Center of Postgraduate Medical Education, Warsaw, Poland; ¹³Department of Surgical Oncology, Transplant Surgery, and General Surgery, Medical University of Gdańsk, Gdańsk, Poland; ¹⁴Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; ¹⁵Research Unit, Sørlandet Hospital, Kristiansand, Norway; ¹⁶Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam; ¹⁷Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna; ¹⁸Department of Internal Medicine, Gastroenterology, and Geriatrics, Klinik Floridsdorf, Vienna; ¹⁹Porto Comprehensive Cancer Center, University of Porto, Porto, Portugal; ²⁰Rede de Investigação em Saúde (RISE), University of Porto, Porto, Portugal; ²¹Centro de Investigação do Instituto Português de Oncologia do Porto (CI-IPOP), University of Porto, Porto, Portugal; ²²Department of Gastroenterology, Hospital Clínic of Barcelona and the Institut d’Investigacions Biomediques August Pi I Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Barcelona; ²³Department of Gastroenterology, University Hospital Álvaro Cunqueiro, Vigo, Spain; ²⁴Department of Hepatology and Gastroenterology, Biogipuzkoa Health Research Institute–Donostia University Hospital, Universidad del País Vasco, CIBERehd, San Sebastián, Spain; ²⁵Department of Gastroenterology, Hospital Río-Hortega, Valladolid, Spain; ²⁶Department of Medicine, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway; ²⁷Department of Medicine, Østføld Hospital, Kalnes, Norway; ²⁸Department of Gastroenterology, Akershus University Hospital, Akershus, Norway; ²⁹Department of Surgery, Horsens Regional Hospital, Horsens, Denmark; ³⁰Department of Surgery, Viborg Regional Hospital, Viborg, Denmark; ³¹Surgical Research Department, Gødstrup Hospital, Gødstrup, Denmark; ³²NIDO Center for Research and Education, Gødstrup Hospital, Gødstrup, Denmark; ³³Department of Surgery, Faculty of Health Sciences, Jagiellonian University, Kraków, Poland; ³⁴Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland; ³⁵Department of Gastroenterology and Hepatology, Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands; ³⁶Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands; ³⁷Department of Gastroenterology and Hepatology, Deventer Ziekenhuis, Deventer, the Netherlands; ³⁸Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands; ³⁹CAUSALab, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston; ⁴⁰Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam

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