DE
Home Offer Syndromes Colon cancer (Colon Ca)

More than 95% of all malignant bowel tumors are colorectal carcinomas; small bowel carcinomas occur only very rarely, accounting for around 2% of all gastrointestinal carcinomas.

Colorectal cancer includes all malignant tumors of the intestine. More than 95% of all malignant bowel tumors are so-called colorectal carcinomas. They affect the appendix (coecum), the colon and/or the rectum. 50% of all colorectal carcinomas affect the rectum, 30% are localized in the sigmoid colon, around 20% are located in the transverse and descending colon and 10% are found in the cecum and ascending colon. Rectal carcinomas develop in the last section of the colon and are located up to 16 centimeters above the sphincter muscle.

In most cases, colorectal carcinomas develop from the cells of the mucous glands within the intestinal wall (adenocarcinoma). Other malignant intestinal tumors are neuroendocrine tumors (carcinoids), lymphomas, sarcomas or squamous cell carcinomas.

Around 2% of all gastrointestinal cancers affect the small intestine. The duodenum, jejunum and ileum are preferentially affected. As with colorectal tumors, most small intestinal cancers are adenocarcinomas.

Epidemiology

The risk of developing the disease increases with advancing age. More than half of all colorectal cancer patients are diagnosed after the age of 70. Only around 55% of all colorectal cancers are diagnosed before the age of 55. Colorectal cancer is the third most common malignant tumor disease in men in Switzerland after prostate and lung cancer and the second most common malignant tumor disease in women after breast cancer. Patients with colon cancer have an approximately 3% better prognosis than patients with rectal cancer.

Causes

The development of colon cancer is a multifactorial process. Seven out of ten cases are sporadic tumors, a quarter of patients have a genetic predisposition and 5% have a hereditary form of colorectal cancer, such as familial adenomatous polyposis (FAP) or hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome).

Pathogenesis

The pathogenesis of colorectal carcinomas is well researched. More than 90% of all colorectal cancers develop from initially benign mucosal polyps (adenomas). The degeneration process, the so-called adenoma-carcinoma sequence, can take several years. Predisposing factors, molecular mechanisms, primary mutations in the APC gene and chromosomal instabilities all play a role during this period. If the complex control mechanisms for cell division and cell growth are impaired, the polypous cells change in an uncontrolled manner. As a result, they no longer remain confined to the mucosa, but grow aggressively and invasively into the surrounding tissue or the entire intestinal wall. They can also spread via the blood and lymphatic fluid and form new foci elsewhere, so-called distant metastases.

Around 5 % of all colorectal carcinomas are caused by Lynch syndrome or hereditary non-polyposis colorectal cancer (HNPCC). HNPCC is inherited as an autosomal dominant trait. Affected individuals have a defect in the mismatch repair genes. As a result, the regulation and correction of DNA mutations are affected. In addition to colorectal cancer, patients with HNPCC often have a higher risk of developing other malignancies, such as breast, ovarian and endometrial cancer. Colorectal cancer is diagnosed in HNPCC around the age of 45.

Very rarely(less than 1%) colorectal carcinomas develop due to familial adenomatous polyposis (FAP). In this precancerous condition, the intestinal mucosa is already riddled with intestinal polyps at a very young age. Inheritance is autosomal dominant. FAP patients have a mutation in the APC tumor suppressor gene on the 5th chromosome. This practically always leads to the development of bowel cancer, usually at a young age.

In addition, there are other syndromes that are also associated with an increased risk of bowel cancer. These include, for example

  • Cowden syndrome
  • Gardner syndrome
  • Juvenile polyposis
  • Peutz-Jeghers syndrome
  • Turcot syndrome

Predisposing factors

The development of adenomas and the resulting colorectal carcinomas is favored by the following, mostly lifestyle-related risk factors:

  • Regularly consuming large amounts of red meat (e.g. pork, beef) or processed meat (e.g. sausages, cured meat)
  • low-fiber diet with little fruit and vegetables
  • physical inactivity
  • overweight and obesity with a high proportion of abdominal fat
  • high alcohol consumption
  • Smoking
  • Older age: the incidence of bowel cancer increases with age
  • Type 2 diabetes mellitus
  • chronic inflammatory bowel diseases such as ulcerative colitis, Crohn's disease and granulomatous colitis
  • Irradiation in the pelvis

Symptoms

Tumors in the colon and/or rectum usually develop slowly. Those affected usually remain symptom-free for a long time. Colorectal carcinomas usually only become symptomatic when the tumor constricts the intestinal lumen due to its size or begins to bleed. The symptoms depend in particular on where the tumour is located. For example, the ascending colon is quite large-lumened and a stenosis is only noticed late. Bleeding mixes with the liquid intestinal contents and is therefore barely visible to the patient. This so-called occult blood can only be detected using certain test methods. The descending colon, on the other hand, has a much smaller lumen and the stool is already semi-solid. A stenosis or obstruction becomes noticeable much more quickly. Typical symptoms of carcinoma in this area are colicky abdominal pain and ileus symptoms as well as visible blood in the stool.

Early symptoms

The first signs of colorectal cancer are usually very unspecific and are often ignored or not considered to be a cause for concern. Typical early symptoms that indicate colorectal cancer are

  • altered bowel habits: very frequent bowel movements, persistent constipation, a constant alternation of constipation and diarrhea and vice versa - also known as paradoxical diarrhea (stool stasis in the stenosis area with bacterial decomposition and fermentation leading to diarrhea)
  • abnormal stool: blood or mucus in the stool, particularly foul-smelling or pencil-thin stool due to intestinal stenosis
  • Other digestive complaints: strong bowel noises and flatulence, flatulence with involuntary defecation (false friend)
  • postprandial nausea or feeling of fullness with only a small amount of food intake
  • Pain: painful bowel movements and cramp-like abdominal pain independent of bowel movements.

In addition, there may be symptoms that generally indicate a tumor disease. This so-called B symptomatology includes unintentional weight loss, a severe reduction in performance, frequent tiredness, as well as repeated mild fever and night sweats.

Late symptoms

Advanced colorectal carcinomas can cause further symptoms. Chronic bleeding from the tumor often leads to blood deficiency anemia. Patients are then pale and tired, have greatly reduced exercise tolerance and react tachycardically to even minor exertion.

Extensive carcinomas have a high energy requirement. In addition, many of those affected can hardly eat due to the gastrointestinal symptoms. Both often lead to pronounced cachexia (tumor cachexia) and massive weight loss.

Larger tumors may be palpable as a hardening under the abdominal wall.

If the carcinoma completely obstructs the intestinal lumen or if the tumor encircles the intestine, ileus is the result. Indicative signs of this are severe, colicky abdominal pain as well as nausea and vomiting. An intestinal obstruction is an emergency and usually requires immediate surgery.

Emergency surgery is also necessary if the carcinoma penetrates the intestinal wall in such a way that it perforates and leads to an acute abdomen. Typical signs of the resulting peritonitis are massive tension in the entire abdominal musculature (sometimes with a hard abdominal wall), severe abdominal pain and impaired intestinal peristalsis (paralytic ileus). If the tumor spreads beyond the intestine or in the case of distant metastases in the liver or other organs, further serious problems can occur. The symptoms depend on the organs and tissues affected and include, for example, colorectal-vesicular and/or colorectal-vaginal fistulas with stool discharge via the bladder or vagina, hepatosplenomegaly with jaundice, ascites and portal hypertension, cough and dyspnoea with pleural and/or pulmonary metastasis and extensive lymphadenopathies.

Special features of rectal carcinoma

The most common initial symptom of rectal carcinoma is blood deposits on the stool or traces of blood on the toilet paper. Any rectal bleeding should therefore be investigated colonoscopically, even in the case of haemorrhoidal disease. This is because it is estimated that around half of all patients with colorectal cancer have haemorrhoids. Other indicative symptoms of rectal carcinoma are tenesmus, compulsion to defecate and a feeling of incomplete bowel evacuation. A persistent foreign body sensation is also frequently described.

Diagnosis

In the early stages, colorectal carcinoma is usually an incidental finding. A quarter of all colorectal cancer patients already have liver metastases at the time of diagnosis.

If colorectal cancer is suspected, the diagnosis begins with a medical history, a laboratory analysis and a clinical examination. This must include a digital rectal palpation - as up to 10% of all colorectal cancers can be palpated. In addition, the stool is examined for blood impurities. Common tests for the detection of occult blood include the guaiac-based Haemoccult test letter and the immunochemical FOB test based on antibodies. This is followed by imaging. The methods of choice are a complete colonoscopy with biopsy as well as rectoscopy and sigmoidoscopy. Sonography, X-ray, computer tomography (CT) and magnetic resonance therapy (MRI) are also used.

Colonoscopy

Colonoscopy with biopsy is considered the gold standard for the diagnosis of suspected bowel cancer. In addition to inspecting the intestinal mucosa, tissue samples can be taken from suspicious areas or small growths such as intestinal polyps can be removed. The bowel must be completely emptied for the examination. If necessary, the patient can be sedated before the examination.

Ultrasound examination of the abdominal cavity: An ultrasound examination shows whether the tumor has already spread beyond the intestine. Metastases in organs such as the liver can also be detected in this way.

Chest X-ray: An X-ray of the chest is taken to detect further tumor metastases, for example metastases in the lungs.

Computer tomography: A CT scan is used if metastases in the lungs or liver are suspected. Sometimes a CT colonography is also used. This virtual colonoscopy makes the colon visible in 2D and 3D images. The disadvantage, however, is the inability to take a biopsy.

Magnetic resonance imaging: An MRI examination is used in rare cases for the targeted search for liver metastases, as these can be better differentiated here than with other methods.

Tumor markers: There are several tumor markers that can be altered in colorectal cancer. A classic tumor marker is the carcinoembryonic antigen (CEA). It is determined before the start of treatment and checked in the course of follow-up care. However, the CEA value is not meaningful enough in all colorectal cancer patients to make treatment decisions dependent on it.

Predictive markers and prognostic factors: There are several predictive and prognostic biomarkers for colorectal cancers. They are particularly important for patients with advanced and metastatic colorectal cancer. For example, BRAF mutations and RAS genes (K-ras) as well as the TNM parameters and the WHO grading system play an important role here. They indicate whether patients will benefit from targeted therapy and provide information about the likely prognosis.

Additional examinations for rectal carcinoma: One of the most important diagnostic tools for rectal carcinomas is the digital rectal examination. However, the examiner can only reach tumors or precancerous lesions that are close to the anus and can be reached with a finger. The rectal examination is usually followed by a rectoscopy (rigid rectoscopy). Tissue samples can also be taken if necessary.

An endosonography can show how far the tumor has already spread. Depending on the situation, a cystoscopy or gynecological examination may also be considered.

Therapy

The treatment of colorectal carcinomas depends on the results of the preliminary examinations and the location, size and spread of the tumor. The earlier a colorectal carcinoma is detected, the better the chances of recovery. Various treatment options are available: Surgery (open surgery as well as laparoscopic minimally invasive or laparoscopic-assisted surgery), chemotherapy and radiotherapy as well as treatment with targeted drugs. Physical procedures such as cryotherapy, thermotherapy, high-frequency and laser procedures are also possible.

Treatment of precancerous lesions and very early tumors: In the case of precancerous lesions and very small, superficial tumors, endoscopic removal (even during the colonoscopy) may be sufficient. The prerequisite for this is that it is actually a precancerous stage or a less aggressive tumor. The carcinoma portion must not make up the entire portion of the removed polyp and the tumor tissue must not have grown into free tissue layers of the intestine. After removal of such early carcinomas, a colonoscopy should be performed again after about six months. Samples are taken from the affected area and examined pathologically.

Treatment for disease confined to the bowel: If not all polyps can be safely removed during the colonoscopy or the pathological examination reveals that the tissue is a rapidly growing tumor, surgery is then performed. The aim is complete surgical resection of the primary tumor.

If colorectal cancer is detected at an early stage (stage I), surgery is curative. Depending on the location of the tumor, the right or left colonic flexure is removed (hemicolectomy) or a transverse resection is performed. The associated lymph nodes are also removed. The intestinal passage is usually restored by suturing the intestinal ends together as an end-to-end or end-to-side ileotransversostomy. In exceptional cases, an artificial bowel outlet (stoma) must be placed. Sometimes the tumor must be reduced in size before the operation. This so-called downsizing or downstaging is carried out using chemotherapy, sometimes combined with radiation of the tumor tissue.

Rectal cancer can also be cured with surgery. Complete removal of the tumor tissue and the adjacent lymph nodes (lymphadenectomy) is crucial for the prognosis. Since the introduction of standardized surgical techniques such as transanal endoscopic microsurgery (TEM) or total mesorectal excision (TME), the otherwise quite high risk of recurrence and the risk of permanent artificial bowel outlets has been considerably reduced. In the case of extensive tumor growth, radio and/or chemotherapy can reduce the size of the tumor as described above, making surgery easier or even possible in the first place. The removed tissue and lymph nodes are examined pathologically. As far as possible, surgical care is taken to maintain a functioning sphincter apparatus and to avoid the creation of a permanent artificial bowel outlet (stoma).

Stoma: If the tumor in a rectal cancer is close to the sphincter or is already very advanced, a complete rectal extirpation must be performed and an artificial bowel outlet created. This does not have to be permanent. Particularly in the case of a very deep bowel resection, where the new suture is placed directly on the sphincter, the suture is often protected by creating a temporary anus praeter. Once the suture has healed (approx. 6 weeks), the artificial anus can often be closed and repositioned. A temporary anus praeter can also be placed as part of an emergency operation in the event of intestinal perforation or inflammatory bowel disease.

Multimodal therapy for metastasis

Adjuvant chemotherapy for colorectal cancer is indicated in the case of R0 resection of liver and/or lung metastases or if there are good prognostic resketability criteria. It should also be ensured that there is no microsatellite instability. Adjuvant chemotherapy should be given as soon as possible after surgery (usually within 8 weeks postoperatively). The drug of choice for stage II patients is monotherapy with fluoropyrimidines. In stage III, there are several first-line therapeutic regimens:

  • FOLFOX: 5-fluorouracil (5-FU) + folinic acid (FA) + oxaliplatin
  • FOLFIRI: 5-FU + FA + irinotecan
  • FOLFOXIRI: 5-FU + FA + oxaliplatin + irinotecan
  • XELOX: capecitabine + oxaliplatin.

With all options, the addition of the VEGF signaling pathway inhibitor bevacizumab improves the effectiveness of the treatment regimen. Cave: The increased toxicity prohibits a combination of bevacizumab with anti-EGFR antibodies (AK).

Special features in subgroups: In the case of molecular pathological gene mutations, therapeutic adjustments are sometimes necessary. For example, anti-EGFR-AK therapy is inefficient in the case of RAS mutations. The following treatment regimens are commonly used clinically:

  • RAS mutation: FOLFOX or FOLFIRI or
  • XELOCRAS wild type and primary tumor of the left colonic flexure: FOLFOX or FOLFIRI or XELOC in combination with anti-EGFR-AK therapy, for example cetuximab or panitumumab
  • BRAF mutation: FOLFOXIRI or inclusion in a therapeutic trial
  • Microsatellite instability: first-line therapy see RAS mutation, followed by a therapy trial with immune checkpoint inhibitors
  • HER2/neu positivity: see RAS or BRAF mutation.

Local ablative methods:

Local ablative methods are an alternative to surgical procedures. Radiofrequency ablation (RFA) is considered, for example, in the case of non-resectable or poorly resectable liver metastases or severely impaired general condition of the patient, particularly after liver resection. Selective Internal Radiation Therapy (SIRT) can be tried in ongoing studies. This radioembolization is primarily intended for patients with disseminated liver metastases for whom there are no other treatment options. Laser-induced interstitial thermotherapy (LITT) may also be suitable for these patients. So far, however, this therapy method has also only been carried out in clinical trials.

Palliative therapy

If the patient's general condition does not permit intensive chemotherapy, there are palliative medical options that can have a positive influence on the course of the disease to a certain extent. Anti-EGFR monotherapy is a possible option for carcinomas in the left colonic flexure or rectal carcinomas of the RAS wild type. Otherwise, combination treatments of 5-FU (or cabecitabine) + bevacizumab or a reduced dose of FOLFOX, FOLFIRI or XELOX (with or without bevacizumab) are possible. In addition, the patient's quality of life should be improved in this palliative situation with analgesic and other necessary symptomatic measures.

Treatment of recurrence

The locoregional recurrence of a carcinoma in the primary tumor area and its lymphatic drainage pathways after an R0 resection is referred to as recurrence. The earlier the recurrence is detected (preferably before it manifests itself), the better the prognosis. In some cases, a recurrence is indicated by an increase in the CEA value. The most important treatment method for recurrence is surgery, but chemotherapy and, particularly in the case of rectal cancer, radiotherapy are also possible.

Prognosis

The earlier the cancer is detected, the better the chances of recovery. The TNM stage and numerous biological factors influence the prognosis. The location of the primary tumor is also relevant. For example, patients with right-sided colon carcinoma, i.e. oral flexura coli sinistra, have a less favorable prognosis in stages III and IV than patients with left-sided colon carcinoma. In addition, right-sided carcinomas more frequently show hypermethylation with the CpG Island Methylator Phenotype (CIMP), hypermutations due to microsatellite instability (MSI) and BRAF mutations. These prognostic differences are less pronounced in stages I and II.

Surgery is the most important therapeutic procedure. If the tumor and adjacent lymph nodes can be completely removed, the chances of recovery are high.

Colorectal carcinomas are most frequently diagnosed in UICC stage III. The average 5-year survival rate is between 40 and 60%. The earlier the diagnosis is made, the better the 5-year survival rate:

  • Stage I: 80 to 100%
  • Stage II: 60 to 80%
  • Stage III: 30 to 60%
  • Stage IV: 0 to 57%.

Prophylaxis

The most important prophylaxis in this country is the possibility of early detection screening, which is covered by health insurance from the age of 50.

General measures

A healthy lifestyle also minimizes the risk of developing bowel cancer. These include

  • regular physical activity
  • avoiding obesity
  • not smoking
  • little alcohol
  • a healthy mixed diet with sufficient fiber and starchy foods (potatoes, cereals, fresh vegetables and fruit)
  • little fat
  • Take vitamins with food (especially A, C, D and E).