Therapy of colon cancer

Therapy of colon cancer

What type of therapy a patient with the diagnosis of rectal carcinoma expects depends very much on the tumor stage and the associated risk of spreading the disease. Earlier, physicians assumed that only tumors in stages I-III were curable. In the meantime, even in stage IV, if there are already secondary tumors (metastases) in other organs, healing can be achieved in some cases.

Therapy in stage I

Rectal carcinomas in stage I include T-stages T1 and T2, ie, tumors that have spread to the muscle layer below the mucosa of the rectum. The only effective therapeutic measure in stage I is surgery. The cancer tissue is to be removed as completely as possible. However, since a greater risk of relapse is present when the tumor is larger, a more extensive operation is necessary in certain cases. Further therapies are not required in stage I, as they show no additional advantages, as studies showed.

• T1 with low risk of relapse
If the tumor is smaller than 3 cm, its cells are largely similar to those of the normal intestinal tissue (good to moderate tissue differentiation) and has not affected any lymphatic or blood vessels, it can usually be complete, with a certain distance Can be excised in the healthy tissue without further interventions being necessary.

• T1 with higher risk of relapse and T2
In the case of larger tumors and tumors, the cells of which have already changed more strongly compared to the normal cells of the intestinal tissue (poor tissue differentiation), there is a higher risk of relapse after the operation. The surgical procedure therefore has to be more extensive in these cases and consists in the so-called mesorectal excision. In addition to the tumor, the surrounding fat and connective tissue, the so-called mesorectum, is also removed. It embeds the rectum in the pelvis and contains blood and lymph vessels. For tumors located in the upper third of the rectum, a partial (partial) mesorectal excision is sufficient; in the case of tumors in the middle and lower rectum thirds, total mesorectal excision is necessary. Then an artificial intestinal outlet (stoma, anus praeter) is usually applied for a certain time in order to temporarily relieve the operating area.
Therapy in stage II and III

Stage II is a larger, more extensive tumor, which may have already affected the lymph nodes. Nevertheless, a cure is possible here, even if there is an increased risk of relapse. Such relapses usually occur either directly locally, at the site of the initial tumor, or affect the liver or lung. Therefore, additional therapies must be carried out in addition to the operation. Especially in tumors in the lower and middle rectal thirds, this is a radiation or radiation chemotherapy preceding the operation. For rectal cancer in the upper third rectum, the use of radiation therapy is still controversial. Here, chemotherapy is recommended after surgery, as is the case with colorectal cancer.

• Colon Cancer Surgery

Also in stages II and III, the goal of the operation is to remove the entire cancer tissue from the body as far as possible. For this purpose, the partial (upper rectal third) or total (middle and lower rectal third) mesorectal excision is used, with which not only the tumor itself, but also the surrounding lymphatics are removed.

•Colon Cancer Radiotherapy before surgery (neoadjuvant)

The tumor itself and the surrounding lymphatic drainage routes are irradiated. This creates a good starting position for the operation and can significantly reduce the risk of a relapse after the procedure. Radiotherapy is performed either with high single doses or more frequently with lower single doses.

•Colon Cancer Radiation chemotherapy before surgery (neoadjuvant)

A combined radiation chemotherapy before the operation represents a greater burden for the patient, but is associated with survival advantages compared to the single radiation therapy. It is therefore recommended especially in the case of larger, locally more advanced tumors, also because the tumor can be significantly reduced before surgery. 5-Fluorouracil (5-FU) is currently the most effective and at the same time well-tolerated chemotherapeutic agent.

• Colon Cancer Chemotherapy after surgery (adjuvant)

Radiochemotherapy followed by surgery may require further adjuvant chemotherapy with 5-FU. However, this only applies if the treating physicians promise further advantages of it and allow the general health of the patient. Chemotherapy works systemically throughout the body and can also damage cancer cells that have already spread.
Therapy in stage IV

While the therapy for stage IV tumors was used only for the purpose of alleviating symptoms, halting the progress of the tumor as long as possible and thus prolonging the survival of patients (palliative therapy), even at this advanced stage, possible. This applies to tumors that have spread to the liver or lungs in such a way that the metastases can be removed surgically: up to a quarter of the affected patients, studies are still cured. Patients with rectal carcinoma in stage IV are therefore divided into three groups with different therapies:

Group 1: Operable hepatic and / or lung metastases
If individual hepatic or lung metastases are completely removed during surgery, the patient has good survival prospects: approximately half of the patients are still alive five years after diagnosis. The surgical procedure is usually combined with chemotherapy three months before and after the operation (therapy regimen FOLFOX: folinic acid, 5-fluorouracil, oxaliplatin), and chemotherapy (treatment regimen FOLFOX) is only possible after surgery.

Group 2: Potentially operable liver and / or lung metastases, symptoms related to the disease or rapid progression of the disease
In some cases large metastases are reduced as a result of a drug therapy so that they can be operated afterwards. There are currently no recommendations on which drugs work best for this purpose. Usually, combinations of different chemotherapeutic agents are used in conjunction with antibodies from the group of targeted therapies, with four to twelve cycles being expected. If metastases become operative, the procedure should be carried out quickly.

Group 3: Many metastases without prospect of operability
In most patients with stage IV rectal carcinoma, a healing operation of metastases in the liver or lung is no longer possible. The therapy is therefore palliative, so it is aimed at the alleviation of physical and mental ailments, which are associated with the tumor suffering. It also serves to delay the progression of the disease in order to prolong the remaining lifetime. However, maintaining quality of life always comes first.

To stop the onset of the disease, drug treatments can be performed with chemotherapy and targeted antibody therapy.

Targeted therapies: Stop tumor growth

Targeted therapies, so-called “targeted therapies”, specifically target specific characteristics and characteristics of the cancer cells, thereby interrupting their growth and multiplication processes. In metastatic rectal cancer, they are usually used in combination with chemotherapy. The following are accepted: bevacizumab, cetuximab and panitumumab.

• VEGF antibody bevacizumab (angiogenesis inhibitor)
Bevacizumab inhibits the effect of blood vessel growth factor Vascular Endothelial Growth Factor (VEGF). This prevents the tumor from being adequately supplied with blood and oxygen and nutrients. It temporarily halts its growth.

• EGFR antibodies cetuximab and panitumumab
On the surface of colorectal cancer cells, binding sites (receptors) are formed for the epidermal growth factor EGF (epidermal growth factor). EGF binds to its receptor and triggers signals that control the growth, division and spread of cancer cells. This binding of EGF to the receptor can be prevented by the antibodies cetuximab and panitumumab. As a result, the signaling pathways for cell growth are interrupted, the cancer cells can no longer divide and spread. However, cetuximab and panitumumab are only effective if a certain genetic change, the so-called KRAS mutation, is not present in the cancer cells, ie, a so-called “KRAS wild-type tumor”.

Installation of an artificial bowel outlet (anus praeter, stoma)

It is not always possible to obtain the natural intestinal output during the operation of colon cancer. Then an artificial bowel outlet (stoma, anus praeter) must be applied. This is necessary if the tumor is very close to the sphincter (anus) or is already well advanced.

When the rectum is completely removed, the lower end of the large intestine is discharged from the abdominal wall in the left lower abdomen. After surgery, there is a 2-3 cm opening, from which a chair can be emptied continuously. It is odorlessly collected in an airtight pouch attached to the skin. However, it is also possible to cover the abdominal wall opening with a flap and to empty the intestine once a day with a flushing liquid. How the bags are changed or the Daremereleerung with a flushing and the skin around the artificial outlet around the nurses, the affected already learn in the hospital. Specialized nurses usually train the affected person thoroughly and are available for questions even after the discharge from the clinic.

In approximately 15% of all operations in rectal carcinoma, an artificial bowel outlet is required. Through the application of special techniques, intestinal connections are still possible at the level of the sphincter, so that in many cases the establishment of an artificial bowel outlet can be prevented. If a tumor is very close to the sphincter, it can be attempted to reduce it by a radio-chemotherapy so far that the maintenance of the normal intestinal discharge can then be attempted. The position, size and extent of the tumor must therefore be clarified exactly in advance of the operation in order to exploit all possible therapeutic possibilities.

However, the establishment of an artificial bowel outlet does not have to be final in any case. For example, it is customary today to protect this seam by the application of an anus praeter in the case of very deep administration, where the new seam connection is applied directly to the sphincter muscle. In such cases, an intermittent (transitory or temporary) anus praeter is used. If the healing of the intestinal seam is completed (about 6 weeks), this anus praeter can be closed again in a small operation. The Darmentleerung then again works naturally. A further possibility of an only temporary artificial bowel exit is in emergency operations, because of intestinal breakthrough or inflammatory diseases. This leads to abdominal inflammation, so that direct reunion of the intestines is associated with the risk of seam fracture. Here, too, the seam can be performed under the protection of an artificial intestinal outlet, or the connecting operation can be performed after healing of the abdominal inflammation.

Sometimes the artificial bowel outlet is also created only to temporarily relieve the operating area. In these cases it can be moved back after a certain time.