Colorectal cancer is the most common cancer of all genders, with more than 40,000 new cases appearing each year and nearly 18,000 deaths. The 5-year survival rate tends to increase because treatments are constantly progressing, thanks to improved surgery and chemotherapy.
The choice of treatment depends on the stage and location of cancer. It is never decided by a single professional but is the result of a multidisciplinary consultation meeting.
The different stages of colorectal cancer
Three criteria are used to determine the extent of colorectal cancer: the size and depth of the tumor, whether or not lymph nodes are involved and the number of lymph nodes affected, and whether or not there is metastasis.
It is on these 3 criteria that the TNM classification (Tumor, Nodes, Metastasis) is based, which determines colorectal cancers in 5 stages of increasing extension/gravity, ranging from 0 to IV :
Stage 0: The tumor is said to be in situ, i.e. it is very superficial and there is no deep or distant invasion.
Stage I: The tumor invades the submucosa, 2nd layer after the mucosa or muscle of the wall of the colon or rectum. The lymph nodes are unharmed and there is no metastasis.
Stage II: Malignant cells have passed through several layers but without lymphatic damage or metastasis.
Stage III: Malignant cells have invaded the lymph nodes near the tumor.
Stage IV: Cancer has spread beyond the colon or rectum, with distant metastases, usually to the liver or lungs.
Different treatments depending on the stage
The goal of the treatment is to cure cancer by eliminating all malignant cells, prevent the tumor from spreading, decrease recurrence, and improve the patient's comfort and quality of life.
There are different types of treatments that will be used depending on the stage of cancer. First, surgery to remove the tumor, radiotherapy for rectal cancers, chemotherapy, and targeted therapies.
Depending on the case, one or more combined treatments will be required. When a complementary treatment is combined with surgery, for example, it is called adjuvant treatment, which is intended to enhance the effectiveness of the main treatment.
Colorectal cancer surgery
The removal of the mesorectum (the fatty area around the rectum that contains the blood and lymph vessels and nerves of the rectum) reduces the risk of recurrence.
In some cases, an ostomy may be necessary. This is an opening made by the surgeon in the abdomen to allow the evacuation of the stool to a special pouch located outside the body.
It may be temporary when it is made to protect the future. When cancer has been completely removed, the operation alone ensures healing.
Surgery combined with radiotherapy
In rectal cancer, pre-operative radiotherapy - possibly combined with chemotherapy - reduces the risk of local recurrence. It is indicated when cancer invades the entire wall and/or if the lymph nodes are affected.
It is the ultrasound endoscopy (examination performed with an endoscope equipped at its tip with an ultrasound probe) that makes it possible to determine the stage of diagnosis. Radiotherapy is most often administered over 5 weeks, at a rate of 5 sessions per week. The surgery takes place 4 to 6 weeks after the last radiotherapy session.
Laparoscopic surgery gives similar results to conventional surgery. It consists of introducing an optical system and instruments through several small incisions.
The surgeon guides his actions by looking at the image that appears on a screen. It has the advantage of reducing the length of hospitalization, limiting post-operative pain, allowing a quicker resumption of activities, and making scars less visible. It has the disadvantage of longer operation time.
Adjuvant chemotherapy
It completes the surgery, reduces the risk of recurrence, and improves survival. Its effectiveness has been demonstrated in the case of colon cancer with lymph node involvement.
There are different chemotherapy protocols that involve different drugs depending on whether or not there are metastases.
The current reference chemotherapy combines 5 FU, folinic acid, and oxaliplatin or "FOLFOX" per 2-day course every 15 days for 6 months. But here again, the protocol will be chosen after a multidisciplinary consultation meeting, with the patient's opinion and agreement.
In cases involving metastases, targeted therapy is currently proposed in addition to chemotherapy. The patient may also be offered the opportunity to participate in a therapeutic trial.
In metastatic forms, chemotherapy should be followed, if possible, by metastatic surgery. The destruction of metastases can possibly be performed by radiofrequency. This technique consists of inserting an electrode into the metastasis and, using radiofrequency waves, heating it to a temperature of more than 60°C. It is thus destroyed by heat. This technique is particularly applicable to metastases located in the liver or lungs.
The contribution of targeted therapies for colorectal cancer
The advent of targeted therapies represents a new advance in the treatment of metastatic colorectal cancer. These are monoclonal antibodies that slow down the growth of the tumor, either by slowing down the formation of vessels that the tumor needs to feed (anti-angiogenic) or by interfering with the development of the tumor (growth factors).
Currently, three targeted therapies are authorized in France for the treatment of metastatic colorectal cancer in combination with chemotherapy. These are bevacizumab marketed under the name Avastin®, an anti-angiogenic agent, cetuximab marketed under the name Erbitux®, which blocks the tumor's cell growth factor (EGFR), and panitumumab whose commercial name is Vextibix®, another anti-EGFR.
Here again, the choice also depends on the decision taken in a multidisciplinary meeting and with the information and agreement of the patient. The choice also depends on the existence or not of certain genetic mutations in the tumor.
Markers and oncogenetic in development
Certain antigenic markers have been used for some years as prognostic indicators. As for ontogenetic, it is a relatively recent discipline that is developing at high-speed thanks to the cooperation of teams dedicated to human genome research and in particular in the field of oncology dedicated to the search for genetic mutations indicating the evolutionary prognosis of the tumor and/or the sensitivity or, on the contrary, the resistance to targeted therapies.
Currently, the search for carcinoembryonic antigen (CEA) can be performed in the initial evaluation of a CRC. ACE is of prognostic interest in metastatic cancers (its increase indicates rapid progression and therefore a poor prognosis, whereas its decrease is predictive of a slower evolution of the tumor).
Concerning mutations (oncogenetic), the search for a KRAS gene mutation (located in human chromosome 12) in a metastatic situation is useful because it is predictive of resistance to anti-EGFR. Thus, its presence is a contraindication to the use of these targeted therapies.
On the other hand, the search for a BRAF mutation (considered an oncogene) is optional because it is not predictive of the non-effectiveness of targeted therapies but is an indicator of poor prognosis.
Colorectal cancer is the subject of many promising research projects, including the evaluation of new therapies (anti-angiogenic, monoclonal antibodies), the search for factors predictive of sensitivity to chemotherapy, or new prognostic markers using molecular biology or proteomics techniques.
Currently, it is recommended by the health authorities to offer patients who so wish the opportunity to participate in clinical trials of new molecules or combinations.
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