G. Argiles¹ , J. Tabernero² , R. Labianca³ , D. Hochhauser⁴ , R. Salazar⁵ , T. Iveson6 , P. Laurent-Puig^7,8,9 P. Quirke¹⁰, T. Yoshino¹¹, J. Taieb^12,7,8,9, E. Martinelli¹³ & D. Arnold¹⁴, on behalf of the ESMO Guidelines Committee*

• ¹Department of Medical Oncology, Vall d’Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona;
• ²Department of Medical Oncology, Vall d’Hebron University Hospital and Institute of Oncology (VHIO), UVic-UCC, IOB-Quiron, Barcelona; Spain;
• ³Department Oncology, Ospedale Papa Giovanni XXIII, Bergamo, Italy;
• ⁴UCL Cancer Institute, London, United Kingdom;
• ⁵Department of Medical Oncology, Catalan Institute of Oncology, Oncobell Program (IDIBELL), CIBERONC, Hospitalet de Llobregat, Barcelona, Spain; 6University Hospital Southampton, NHS Foundation Trust, Southampton, United Kingdom;
• ⁷Assitance PubliqueHôpitaux de Paris AP-HP Paris.Centre, Paris;
• ⁸Paris Cancer Institute CARPEM, Centre de Recherche des Cordeliers, Paris Sorbonne University, Paris University, Paris;
• ⁹ INSERM, CNRS, Paris, France;
• ¹⁰Pathology and Data Analytics, School of Medicine, University of Leeds, Leeds, United Kingdom;
• ¹¹National Cancer Center Hospital East, Kashiwa, Japan;
• ¹²Department of Gastroenterology and GI Oncology, Georges Pompidou European Hospital, Paris Descartes University, Paris, France; 13Università degli Studi della Campania Luigi Vanvitelli, Department of Precision Medicine, Naples, Italy;
• ¹⁴Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Germany

INTRODUCTION

Incidence and epidemiology

Colorectal cancer (CRC) is the third most common tumour in men and the second in women, accounting for 10% of all tumour types worldwide. Incidence is 25% higher in males and differs greatly between countries. With more than 600,000 deaths estimated each year, CRC is the 4th most common cancerrelated cause of death globally [1-2]. The growing incidence in some countries reflects a modification in lifestyle and its consequences related with ‘Westernisation’ such as obesity, physical inactivity, alcohol consumption, high red meat intake and cigarette smoking [3]. Some data suggest a putative role in colon cancer carcinogenesis for factors that cause imbalances in gut microbiota [4, 5].

The mortality rate in the European Union is 15–20 out of 100 000 in males and 9–14 out of 100 000 in females and has decreased over time, particularly in females. In affected European individuals, 5-year survival ranges from 28.5% to 57% in men and from 30.9% to 60% in women, with a pooled estimation in 23 countries of 46.8% in men and 48.4% in women [6].

The risk of developing colon cancer depends on factors which can be classified into lifestyle or behavioural characteristics and genetically-determined factors. Screening tests are modulated according to the individual probability of developing CRC [7-9]. Age is considered the major unchangeable risk factor for sporadic colon cancer: nearly 70% of patients are >65 years of age and this disease is rare before the age of 40 years, even though data from Western registries show an increased incidence in the 40–44 year-age group [10].

Individuals with any of the following are considered at high risk of colon cancer and must be actively screened and in case of inherited syndromes, also referred for genetic counselling (see ESMO guidelines for hereditary gastrointestinal cancer [11]):

• a medical history of adenoma, colon cancer, inflammatory bowel disease (Crohn’s disease and ulcerative colitis);
•  significant family history of CRC or adenoma;
• an inherited cancer syndrome (2%–5% of all CRC), such as familial adenomatous polyposis coli and its variants (1%), Lynch-associated syndromes (hereditary non-polyposis colon cancer) (2%–4%), Turcot, Peutz-Jeghers and MUTYH-associated polyposis syndrome.

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