Result card

  • CUR6: What is the natural course of CRC?

What is the natural course of CRC?

Authors: Mirjana Huic, Eleftheria Karampli, Silvia Florescu, Cipriana Mihaescu-Pintia

Internal reviewers: Laura Cacciani, Sophie Brunner, Esther Kraft

Most colon cancers arise from non-malignant adenomas in form of adenomatous polyps. Genetic steps from polyp to dysplasia to carcinoma in situ is defined (the adenoma-carcinoma sequence) (point mutation in K-ras proto-oncogene, hypomethylation of DNA leading to enhanced gene expression, allelic loss of tumour suppressor APC gene, allelic loss at DCC gene (deleted in colon cancer) on chromosome 18, and loss and mutation of p53 on chromosome 17 {1-3}.


Due such natural course, CRC is particularly suitable for screening. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. Adenomas are most often polypoid, but can also be sessile or flat. An adenoma grows in size and can develop high-grade neoplasia. At a certain point in time, the adenoma can invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms yet (preclinical). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed {1-3}.


In developed countries, approximately, 40.50% of the population develop one or more adenomas in a lifetime, but the majority of these adenomas will never develop into CRC. Only 5.6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is unobserved, but is estimated to take at least 10 years. This long latent phase provides an excellent window of opportunity for early detection of the disease. When detected in the adenoma-phase, removal of the adenoma can prevent the incidence of CRC. But even when detected as an early-stage cancer, prognosis is considerably better than for late-stage cancer {1-3}.


An adenoma is benign, dysplastic tumour of columnar cells or glandular tissue. They have tubular, tubulovillous or villous morphology. The likelihood of an adenoma being present increase with age. At the age of 60-70, 5% of asymptomatic subject will have a polyp of >1 cm, or cancer with no symptoms, and up to 50% will have at least one small<1cm adenoma {1-3}.

Removal of adenoma at colonoscopy and subsequent surveillance reduces the risk of development of colon cancer by approximately 80%. The remaining 20% are either newly formed, missed, or difficult to detect, e.g. flat adenoma.


About 5% of CRC have well defined single gen basis. Onset of cancer is earlier than in sporadic cases, at age 40-50 or younger {1-3}.

Huic M et al. Result Card CUR6 In: Huic M et al. Health Problem and Current Use of the Technology In: Jefferson T, Cerbo M, Vicari N [eds.]. Fecal Immunochemical Test (FIT ) versus guaiac-based fecal occult blood test (FOBT) for colorectal cancer screening [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali; 2014. [cited 17 August 2022]. Available from: