Colorectal cancer is the third most common cancer in the world with more than 19.9 million new cases in 2020 . Incidence is higher in males than females and differs greatly between countries. The growing incidence in some countries reflects modification in lifestyle and its consequences related with ‘Westernisation’ such as obesity, physical inactivity, alcohol consumption, high red meat intake, and cigarette smoking [2, 3]. Some data suggest a putative role in colon and rectal carcinogenesis for factors that cause imbalances in gut microbiota [4, 5]. Other risks factors for colorectal cancer include inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and genetic disorders which typically represent less than 5% of cases [6, 7].
Colorectal cancer starts in the colon or rectum, and they are often grouped together because they have many features in common. Colon cancer, as is the case for rectal cancer, typically affects older individuals, though it may occur at any age. It usually begins as, noncancerous (benign) clumps of cells called polyps that form on the inside of the colon. Over time some of these polyps may become cancerous. Polyps may be small and produce few, if any, symptoms, therefore screening tests are essential for prevention of disease development . Screening tests are conducted according to individual probability of developing colon cancer. Age is considered the major unchangeable risk factor for sporadic colon cancer with nearly 70% of patients being over 65 years of age. There is now decreasing incidence of colorectal in older populations, but the incidence has nearly doubled in younger adults since the early 1990s. Approximately 1 in 10 new diagnoses are now seen in individuals 50 years or younger .
Rectal cancer is cancer that begins in the rectum. The rectum is the last part of the large intestine. It starts at the end of the final segment of the colon and ends when it reaches the short, narrow passage leading to the anus . Rectal cancer, as is the case for colon cancer, is preventable, with screening tests being of immense importance for prevention of disease development. Nearly all rectal cancer develops from rectal polyps, which are benign growths on the rectal wall. Detection and removal of these polyps by colonoscopy reduces the risk of rectal cancer . Screening tests are conducted according to individual probability of developing rectal cancer. Median age at diagnosis is ~70 years, but predictions suggest that this figure will rise in the future .
A family history of colorectal cancer can increase the risk of an individual developing colorectal cancer over a lifetime therefore risk assessment is of valuable importance. The heritable component of colorectal cancer is around 35% . Familial colorectal cancer results from the interaction of genetic and environmental causes. There is evidence that colonoscopy for screening purposes should be repeated at five-year intervals in people with a family history of colorectal cancer . Several genetic variations have also been identified that are associated with colorectal cancer including high-risk genetic syndromes such as Lynch syndrome, familial adenomatous polyposis (FAP, rare), and MUTYH-associated polyposis (MAP, rare). The screening interval can be even shorter in patients with high-risk genetic syndromes, with individuals with FAP receiving colonoscopy annually starting around 10 to 12 years of age .
Whether the colon cancer can be cured depends on several factors including the size and location of the tumour, the cancer’s stage when detected, whether the cancer is recurrent and the individual’s overall health [16, 17]. Normally, the only way to cure colon cancer is surgery with resection of the affected bowel segment and supplementary blood and lymph nodes, and possibly complete resection of metastases, if any.
Upon diagnosis, colon cancer may be localized or metastatic. For localized colon cancer, surgical resection is the only curative modality that is often combined with chemotherapy to destroy potential micrometastases outside the resected area, reduce the likelihood of disease recurrence, and increase cure rates [17, 18]. Micrometastases is a small number of cancer cells that have spread from the primary tumour site to other parts of the body, but they are too few to be detected in screening or diagnostic tests.
However, approximately 20% to 25% of newly diagnosed colon cancers are metastatic at diagnosis (simultaneous metastasis), while others may develop metastatic disease after treatment for local disease . The liver is the dominant site for metastasis in patients with colorectal cancer, followed by the lungs, lymph nodes, and peritoneum . After being diagnosed, patients should be considered within a multidisciplinary team with the goal being to achieve resectable (able to be removed by surgery) disease. Medically fit patients with a limited number of metastases in the liver and/or lung are candidates for potentially curative resection of the metastases. Other local treatments such as ablation therapy (a technique that uses very high or low temperatures to destroy abnormal tissue or tumours) or stereotactic radiation therapy could be used as a supplement to surgery and can be an alternative to liver resection. In addition, patients can be treated with neoadjuvant therapy (treatment prior to main therapy) to eliminate potential micrometastases before surgery [16, 17]. Following resection, patients may be observed or be offered adjuvant (therapy applied after initial treatment) chemotherapy with or without biologic treatment [16, 17].
However, most patients with metastatic disease are not surgical candidates therefore, for these patients, upfront chemotherapy with or without targeted therapy and immunotherapy with the goal of conversion to a resectable state in recommended [16, 17]. In case conversion fails, there is a number of systemic therapies that can be considered. Systemic treatment of non-operable disease aims to prolong life, relieve symptoms, and maintain quality of life [17, 19]. The treatment strategy will depend on whether a rapid response is desirable due to symptoms or tumour-associated complications [17, 20], or the treatment primarily aims to prevent further progression and extend life. Where prompt response is desired, combination chemotherapy given as infusion regimens with antibody is recommended. With less intensive therapy, monotherapy can be started and later followed by combination therapy [17, 21-24]. Molecular pathological examination is crucial for the choice of treatment and is recommended to be performed in all patients who have a widespread disease and who are eligible for systemic therapy including RAS mutations, BRAF mutations, MSI/dMMR and DPYD-loss.
Most of the cancers arising in the rectum are adenocarcinomas. The optimal approach to treating rectal adenocarcinoma depends on several factors, of which the location in the rectum, and the local disease extent are the most important. Surgery is the only curative treatment for rectal cancer. In patients with limited invasive cancer in a polyp with no adverse features, surgical removal of the polyp alone may be sufficient. However, in patients with locally extensive, fixed, bulky tumours; extensive nodal disease; or extramural venous invasion a more radical approach that includes four months of upfront chemotherapy and either long-course chemoradiotherapy or short course radiotherapy prior to surgery may be attempted [17, 25]. All patients with invasive rectal cancer should be discussed in a multidisciplinary team.
Approximately 50% to 60% of patients diagnosed with colorectal cancer will develop metastases at some point during the patient’s journey . The management of patients who have simultaneous metastatic disease must be individualized with the most crucial factors being resectability of the metastasis and whether the primary tumour is symptomatic or not . In cases when both the primary tumour and metastases are resectable, one approach is to start with chemotherapy and then short-course radiation therapy to the primary tumour including involved nodes followed by simultaneous resection of the primary and metastatic disease. Whether resection of the metastases is performed simultaneously or in a sequential procedure depends on several factors, including the extend of resection of the primary and metastatic tumours and the patient’s general condition .
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