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      Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

      research-article
      1 , 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 1 , 22 , 2 , 23 , 24 , 25 , 26 , 27 , 22 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 1 , 7 , 36 , 11 , 24 , 33 , 37 , 38 , 39 , 22 , 40 , 41 , 42 , 43 , 1 , 44 , 45 , 46 , 7 , 47 , 19 , 48 , 49 , 23 , 50 , 51 , 52 , 42 , 53 , 54 , 55 , 49 , 1 , 56
      Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
      Recommendation, Clinical, Young, 50 Years, Colorectal Cancer

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          Abstract

          BACKGROUND & AIMS:

          Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC.

          METHODS:

          After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%.

          RESULTS:

          The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients.

          CONCLUSIONS:

          The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.

          Graphical Abstract

          This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e7. Upon completion of this module, successful learners will be able to evaluate high-risk symptoms of early-onset colorectal cancer, explain the utility of tumor testing and germline testing in this setting, integrate the oncological management with the fertility management, and cite the surveillance protocol after cure from colorectal cancer <50 years.

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          Most cited references262

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          ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.

          Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.
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            Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society

            In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250-281. © 2018 American Cancer Society.
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              Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial.

              Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale randomised trials to support its use. We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes. Between July, 1996, and July, 2002, we undertook a multicentre, randomised clinical trial in 794 patients with colorectal cancer from 27 UK centres. Patients were allocated to receive laparoscopic-assisted (n=526) or open surgery (n=268). Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins, proportion of Dukes' C2 tumours, and in-hospital mortality. Analysis was by intention to treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN74883561. Six patients (two [open], four [laparoscopic]) had no surgery, and 23 had missing surgical data (nine, 14). 253 and 484 patients actually received open and laparoscopic-assisted treatment, respectively. 143 (29%) patients underwent conversion from laparoscopic to open surgery. Proportion of Dukes' C2 tumours did not differ between treatments (18 [7%] patients, open vs 34 [6%], laparoscopic; difference -0.3%, 95% CI -3.9 to 3.4%, p=0.89), and neither did in-hospital mortality (13 [5%] vs 21 [4%]; -0.9%, -3.9 to 2.2%, p=0.57). Apart from patients undergoing laparoscopic anterior resection for rectal cancer, rates of positive resection margins were similar between treatment groups. Patients with converted treatment had raised complication rates. Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes. However, impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use.
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                Author and article information

                Journal
                101160775
                31839
                Clin Gastroenterol Hepatol
                Clin Gastroenterol Hepatol
                Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
                1542-3565
                1542-7714
                20 June 2024
                March 2023
                20 December 2022
                26 June 2024
                : 21
                : 3
                : 581-603.e33
                Affiliations
                [1 ]Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [2 ]Department of Gastroenterology, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
                [3 ]Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
                [4 ]Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, California
                [5 ]Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, Illinois
                [6 ]Gastrointestinal Endoscopy Unit, Humanitas University, Humanitas Research Hospital, Rozzano, Italy
                [7 ]Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, and Department of Hematology Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
                [8 ]Faculty of Medicine and Medical Technology, University of Tampere and TAYS Cancer Centre, Arvo Ylpön katu, Tampere, Finland
                [9 ]Unit of Gastroenterological Surgery, Tampere University Hospital, Elämänaukio, Tampere, Finland
                [10 ]Applied Tumor Genomics Research Program and Department of Surgery, Helsinki University and Helsinki University Hospital, Helsinki, Finland
                [11 ]Department of Radiology, Radiation Oncology and Hematology, Università Cattolica del Sacro Cuore di Roma, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy
                [12 ]Department of Medicine, Division of Gastroenterology, University of California San Diego, San Diego, California
                [13 ]Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania
                [14 ]Department of Medical Oncology. Amsterdam UMC, Location de Boelelaan, Amsterdam, The Netherlands
                [15 ]Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio
                [16 ]Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
                [17 ]SOC Gastroenterologia Oncologica e Sperimentale Centro di Riferimento Oncologico di Aviano (CRO) IRCCS 33081, Aviano, Italy
                [18 ]Oncology Department, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [19 ]Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
                [20 ]Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary’s Hospital, Manchester, United Kingdom
                [21 ]Division of Gynaecology, St Mary’s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
                [22 ]Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
                [23 ]Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [24 ]Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway
                [25 ]Department of Medicine, Division of Hematology and Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
                [26 ]Department of Molecular Diagnostics & Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, California
                [27 ]Department of Surgery and Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
                [28 ]Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
                [29 ]Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
                [30 ]Division of Digestive and Liver Diseases, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center and the Vagelos College of Physicians and Surgeons, New York, New York
                [31 ]Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany
                [32 ]Department of Medicine and Surgery, University of Parma, Parma, and Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy
                [33 ]Lynch Syndrome Clinic, Centre for Familial Intestinal Cancer, St Mark’s Hospital, London North West University Healthcare NHS Trust, Harrow, United Kingdom
                [34 ]Department of Colorectal Surgery and Edward J. DeBartolo Jr Family Center for Young-Onset Colorectal Cancer, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
                [35 ]Department of Gastroenterology, M. D. Anderson Cancer Center, Houston, Texas
                [36 ]IFOM ETS - The AIRC Institute of Molecular Oncology, Milan, Italy
                [37 ]Faculty of Medicine, Department of Surgery & Cancer, Imperial College, London, United Kingdom
                [38 ]Surgical Center for Hereditary Tumors, Ev. BETHESDA Khs. Duisburg, Academic Hospital University of Düsseldorf, Düsseldorf, Germany
                [39 ]School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas
                [40 ]Young-Onset Colorectal Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
                [41 ]Medical Oncology, AULSS 5 Polesana, Santa Maria Della Misericordia Hospital, Rovigo, Italy
                [42 ]Centro Scienze della Natalità, Department of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute, Milano, Italy
                [43 ]University of Colorado Anschutz Medical Center and Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado
                [44 ]Pathology Unit, Mater Salutis Hospital, ULSS9, Legnago, Verona, Italy
                [45 ]Department of Medical and Surgical Sciences, Universita degli Studi di Bologna, Bologna, Italy
                [46 ]Department of Onco-Haematology, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
                [47 ]Department of Medicine, Section of Gastroenterology, VA Boston Healthcare System and Boston University, Boston, Massachusetts
                [48 ]Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio
                [49 ]Brigham and Women’s Hospital, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts
                [50 ]Chirurgia Generale 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University Hospital of Padova, Padova, Italy
                [51 ]Hereditary Cancer Program, Catalan Institute of Oncology, Oncobell Program, Bellvitge Biomedical Research Center (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
                [52 ]Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Madrid, Spain
                [53 ]Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas
                [54 ]Unit of Hereditary Digestive Tract Tumours, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
                [55 ]Department of Colon & Rectal Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
                [56 ]Division of Gastroenterology and Hepatology, Department of Internal Medicine and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan
                Author notes
                [*]

                Authors share co-first authorship.

                [‡]

                Chairs of the Working Panels.

                Correspondence Address correspondence to: Giulia Martina Cavestro, MD, PhD, Via Olgettina 60, Milan 20132, Italy. cavestro.giuliamartina@ 123456hsr.it .
                Article
                NIHMS2000482
                10.1016/j.cgh.2022.12.006
                11207185
                36549470
                c30e6d10-e6d2-4e0e-933b-8e0e76645b2b

                This is an open access article under the CC BY-NC-ND license ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

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                recommendation,clinical,young,50 years,colorectal cancer
                recommendation, clinical, young, 50 years, colorectal cancer

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