Colorectal cancer/therapy



The method of treatment of KR-CA can only be determined after a complete examination of the patient and determination of the staging of the disease. Each patient should be consulted at an indication seminar, and the resulting treatment should be the result of a consensus of an oncologist, surgeon, gastroenterologist, and possibly also a pathologist. The therapeutic procedure must also always depend on the patient's general state of health and his wishes.

Treatment modalities used to treat KR-CA include endoscopic', surgical and oncological methods. As a rule, the tumor mass is removed first, either endoscopically or, more often, surgically, followed by systemic oncological treatment. In the case of extensive tumors, surgery is preceded by neoadjuvant oncological therapy.

Therapy procedures for KR-CA located in the colon and in the rectum differ slightly.

Endoscopic treatment
Its importance is irreplaceable, especially in the diagnosis of diseases and the subsequent dispensary of patients after treatment. It is mainly used for curative treatment of precancers' (adenomas) or very early stages of KR-CA (carcinoma in situ, pT1), or for palliative treatment to open intestinal stenoses caused by a tumor (insertion of a stent).

Curative treatment Depending on the extent of the lesion, we use:
 * polypectomy' (EPE),
 * endoscopic mucosal resection' (EMR),
 * endoscopic submucosal dissection (ESD) - removal of the polyp together with the submucosa.

In patients with a diagnosis of KR-CA pT1, we decide between an endoscopic or surgical solution based on other parameters. Endoscopic treatment is sufficient for benign tumors, however, for so-called high-risk pT1 carcinomas, we proceed with a subsequent surgical solution. High-risk cancer criteria: In these patients, we perform surgical resection with radical lymphadenectomy, as well as in more advanced stages of KR-CA.
 * incomplete removal or partial removal (not en block);
 * distance from resection margins 1 mm and less;
 * low differentiation;
 * evidence of invasion into lymphatic vessels in a histological specimen.

The application of a metallic stent is used either for acute intestinal obstructions to wait out the time for an operative solution, or for inoperable and generalized carcinomas in the last stages to improve the patient's quality of life. However, according to various studies, the usefulness of these procedures is somewhat questionable. It should only be used in carefully indicated cases after interdisciplinary consultation. Patients indicated for biological treatment bevacizumab have been shown to have a higher risk of perforation.
 * Palliative treatment

Surgical treatment
Still the only curative treatment for colorectal cancer is ``oncoradical resection'' (with the exception of very early stages that can be resolved endoscopically, see the previous paragraph). It is indicated whenever it is possible to perform a 'curative radical (R0) resection, i.e. to remove the entire tumor mass. Possibly also for palliative reasons, similar to endoscopic treatment, to open the intestinal lumen and thereby prolong and improve the patient's quality of life.

For colon cancer, we use radical resection of the affected section of the intestine together with the removal of the hinge (mesocolon). The advantage of this procedure is the removal of a larger number of lymph nodes (at least 12), the removal of potentially tumor-damaged tissue and the limitation of postoperative tumor spread. Radicality is observed even in the earlier stages (T1, T2). If the tumor is unfavorably located in the watershed of two supplying arteries, we proceed to even more radical procedures - "extended resection" or "subtotal colectomy" (removal of the entire colon, leaving the rectum and establishing an ileorectal anastomosis). The distance at the aboral end should be at least 5 cm from the tumor. The extent of resection is determined by the extent of dissection of the lymph nodes (and vessels) along the arterial supply, when the ligation occurs near the distance between the arterial trunks (high ligature): Laparoscopic approach is a used alternative to the classic procedure, especially for left-sided colon tumors.
 * Resection of the colon
 * right hemicolectomy - ligature of a. ileocolic, a. colica dextra and ramus dexter arteriae colicae mediae'' (tumor of the ascending colon);
 * extended right hemicolectomy - ligature of a. ileocolic, a. colica dextra and additionally a. colica media (for tumors 'flexura coli dextra);
 * left hemicolectomy - ligature of a. colica sinistra (descending colon tumor);
 * extended left hemicolectomy - ligature of a. colica sinistra and a. colica media (tumor at the flexura coli sinistra);
 * sigma resection - ligatures a. mesenterica inferior.

The most used procedure is 'total mesorectal excision (TME), which significantly reduces the occurrence of local recurrences. The prognostic factor for the success of TME is mainly the positivity of the resection margins. Nowadays, we use modern mini-invasive, robotic and laparoscopic methods, which, however, are still radical enough, but at the same time less mutilating for the patient. Surgical procedures can be divided into:
 * Resection of the rectum
 * Curative powers' (potentially):
 * 1) standard operation – resection recta (+ mesorecta), can be with sphincter amputation, but also sphincter-preserving (even that is sufficiently oncoradical);
 * 2) extensive surgery – resection of the rectum, mesorectum and abdominopelvic lymph nodes and vessels;
 * 3) ultra-extensive surgery - additionally with resection of the internal iliac vessels.


 * Palliative procedures consist of:
 * 1) tumor removal - in most cases it is better to remove the tumor, even if curative resection is excluded due to the staging of the disease or the general condition of the patient, every growing tumor threatens the patient with the formation of an ilea, perforation of the intestinal wall, tumor disintegration (necrosis);
 * 2) solving an obstruction in the passage of the intestine (it is a tumor) - with a stoma or bypass;
 * 3) pain treatment.

The liver is the organ where we most often find KR-CA metastases, and their treatment is closely related to the patient's prognosis.
 * Resection of liver metastases


 * Standard preoperative examination
 * Colonoscopy with biopsy - if this is not possible then double-contrast irrigography,
 * sonography of the liver
 * CT of the liver – in case of an unclear finding or finding of liver metastases on sono,


 * CT of small pelvis,
 * X-ray lung
 * CT lung – when metastases are found on X-ray
 * bronchoscopy – when metastases are suspected, to rule out duplication,


 * urological examination - in case of hematuria or urological problems with suspicion of disease progression,
 * gynecological examination',
 * determination of oncomarkers' - CEA, CA 19–9,
 * for rectal cancer: transrectal sonography', anorectal manometry.

Oncology treatment
Almost every patient with KR-CA undergoes oncological treatment in one of its forms - radiotherapy, chemotherapy, biological treatment. According to the treatment sequence, we distinguish between neoadjuvant, adjuvant and separate oncological treatment. Radiotherapy is particularly useful for rectal cancer, as it is highly sensitive to it and, in addition, has a high susceptibility to locoregional spread (colon cancer is more likely to establish distant metastases), we apply a dose of 30 Gy.

We use neoadjuvant treatment especially for rectal cancer - either radiotherapy alone or in combination with chemotherapy (ie chemoradiotherapy). In the case of extensive tumors (T3–T4, N+), during neoadjuvant (preoperative) treatment there is a 'decrease in the tumor mass (so-called downstaging), and thus a better operability of the findings (a higher percentage of sphincter-preserving surgeries), an increase in the percentage of curative resections and a lower incidence of local recurrences. However, the overall longer survival of patients undergoing neoadjuvant therapy was not confirmed. The combination of chemo- and radiotherapy is accompanied by somewhat higher toxicity. In general, we have to consider the indication of neoadjuvant therapy in relation to the patient's condition, so that it does not significantly worsen his quality of life. The chemotherapy of choice is 5-fluorouracil (5-FU), an alternative is capecitabine (po), possibly in combination with oxaliplatin or irinotecan. . Primarily in combinations like FOLFOX (leukovorin, 5-FU, oxaliplatin).
 * Neoadjuvant treatment

Leucovorin is a biomodulator and is added to enhance the effect of 5-FU and reduce toxicity.

Adjuvant treatment If it is necessary after surgical treatment, systemic treatment comes next, the aim of which is to remove possible micrometastases, prevent further spread of the disease or possible relapse. The decision to start adjuvant treatment is again based on the patient's condition and tumor characteristics. It is generally recommended especially for stage III, where it increases long-term survival without signs of disease by up to 30%, and for stage II tumors with a high risk of recurrence. Adjuvant chemotherapy improves 5-year survival by 10%.

We use palliative stand-alone oncological treatment in patients with inoperable advanced findings, extending both the median of disease progression and also the median survival.
 * Separate oncological treatment

A novelty in the treatment of KR-CA in the last 10 years is the introduction of targeted therapy, sometimes also referred to as biological therapy. When applied together with chemotherapy, it increases its effectiveness (increasing treatment response and prolonging the median survival of patients). The principle of targeted treatment is influencing specific signaling pathways necessary for tumor growth. In the Czech Republic, three drugs are now used for targeted treatment: "bevacizumab" (an antibody against vascular endothelial growth factor A - VEGF-A), "cetuximab" and "panitumumab" (receptor inhibitors for epidermal growth factor – EGFR).
 * Targeted treatment

Summary
General risk factors:
 * less than 12 resected lymph nodes;
 * low degree of tumor differentiation (grade 3 and 4);
 * tumor growth through the entire intestinal wall (T4);
 * intestinal perforation or obstruction as the primary manifestation of the tumor;
 * angioinvasion, lymphangioinvasion or perineural invasion;
 * unknown resection margins;
 * increased level of carcinoembryonic antigen (CEA);
 * mucinous component of the tumor.

Treatment strategy according to disease staging at the time of diagnosis:

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