Colon cancer

Cancer of the colon – one of the most common malignant tumors, the incidence is growing every year more and more. The structure of oncological disease, colorectal cancer ranks fourth as the structure of cancer death – second place in women (after breast cancer) and third place in men (after prostate and lung cancer). Over the past 20 years, treatment of malignant tumors of the colon has undergone significant changes. Modern methods of diagnosis can improve the accuracy of preoperative staging of tumor process and thus optimize treatment. In addition, significantly expanded the arsenal of drugs used to treat metastatic colorectal cancer forms. About contemporary approaches to diagnosis and treatment of this pathology, we told the doctor of medical sciences of the Institute of Oncology AMS of Ukraine Elena Kolesnik.

- Actual question is whether the problem of colorectal cancer for our country?
- The incidence of colorectal cancer in Ukraine is quite high – 34.9 cases per 100 thousand population. This is the greatest indicator of all the CIS countries. In the structure of mortality from malignant neoplasms in Ukraine, this pathology is one of the leading positions after lung cancer, stomach and breast cancer. Unfortunately, so far about a third of all cases of colorectal cancer is detected in advanced stages of disease. Shortcomings in the diagnosis and treatment leads to the fact that 35-45% of all patients with malignant tumors of the rectum and colon do not live a year from diagnosis. Thus, the provision of care to patients with colon cancer remains an important challenge for the health system of Ukraine. The most pressing issues are timely diagnosis and adequate provision of special treatment, which increases survival of patients with colon cancer (the European average five-year overall survival – 50%).

- What should be the algorithm of examination of patients with suspected colon cancer?
- Suspect the presence of malignancy allow first complaint of the patient and medical history. Clinical manifestations of colorectal cancer depend on the localization of primary tumor and manifest complications arising from tumor growth. The main symptoms are intestinal bleeding and disruption of normal bowel function (constipation, diarrhea).
Algorithm for examination of a patient with similar complaints should include:
- Clinical examination, including study of finger rectum;
- Endoscopic examination of the colon (sigmoidoscopy or colonoscopy) with biopsy of the tumor;
- Radiography of the colon with contrast barium;
- Endorectal ultrasonography for tumors of the rectum;
- Ultrasound / CT of the liver;
- CT / MRI of the pelvis at a fixed tumor of the rectum;
- Chest x-rays (if necessary, CT);
- Laboratory tests, including determination of the level of tumor marker CEA in the blood serum;
- Other studies – on the grounds.
The use of the aforementioned techniques can verify the diagnosis, determine the true incidence of tumor process and stage of disease, to choose adequate treatment policy, to select patients with solitary liver and lung metastases to perform surgery.
Unfortunately, to date, doctors practice medical networks do not always have the opportunity to use all of the above diagnostic methods.
Methods of diagnosis of tumors of the colon is constantly improving, developing new technologies. For example, a promising method for diagnosing colorectal cancer is a virtual colonoscopy, the sensitivity of which, according to foreign authors, leaves 75-100%.

- It is known that the main method of treatment of patients with colon cancer surgery. What are the methods of preventing relapse and in what cases they should be used?
- Of course, radical removal of the tumor – the first and most important task of any surgical intervention. Unfortunately, even after radical surgery of at least 50% of patients die at different times due to the appearance of distant metastases, which allows to conclude that the presence of systemic disease at the time of surgical treatment. Chemotherapy is an integral part of the combined and complex treatment of II-IV stages of colorectal cancers. More than 70% of patients with colon cancer at various stages of treatment used with adjuvant chemotherapy or palliative purpose. There are literature data indicating that tumor cells can circulate in the blood of all patients with localized forms of colon cancer.
The highest risk of distant metastasis exists in patients with presence of metastases in regional lymph nodes (III stage) and the germination of a tumor in the adjacent fatty tissue or adjacent organs (II stage), as well as the presence of a number of other adverse prognostic factors. So, have a poor prognosis, patients with distant metastases, large tumor size, marked anemia, high levels of lactate dehydrogenase and carcinoembryonic antigen. The presence of complications such as bowel obstruction or perforation, also negatively affects the survival of patients.
In these patients surgical treatment must be complemented by adjuvant therapy, aimed at the destruction of micrometastases in order to prevent recurrence of the disease.
Since the 1980’s the only drug from randomized studies that have demonstrated its effectiveness in the adjuvant treatment of colorectal cancer were from the group of antimetabolites fluoropyrimidines, particularly 5-fluorouracil. Currently, adjuvant therapy 5-fluorouracil (with leucovorin) remains the most common among oncologists. The duration of therapy is 6 months. Infusion of 5-fluorouracil with high-dose leucovorin (mode de Gramont) most effective and safe in comparison with the jet.
In the last decade, a number of new drugs with high antitumor activity. Capecitabine, oral fluoropyrimidines, has been tested in randomized trials as a drug adjuvant therapy. Relapse-free survival of patients with colon cancer stages II-III after treatment with capecitabine was slightly better than 5-fluorouracil, with the marked decrease in the number of side effects, which allowed to recommend the drug for adjuvant therapy.

- Does the armory of oncologists today a new, more effective schemes of adjuvant therapy for patients with colon cancer?
- In the past two years there have been significant changes in the adjuvant treatment of colon cancer when treatment regimens began to use the drug oxaliplatin (Элоксатин ®). Oxaliplatin has been well studied in the schemes of treatment of metastatic colorectal cancers. It was shown that oxaliplatin has a synergy of action with respect to 5-fluorouracil and leucovorin in the absence of cross-resistance. Three randomized studies have shown the effectiveness of oxaliplatin in the adjuvant mode in patients with colorectal carcinoma.
The most significant was a multicenter international study MOSAIC.
MOSAIC study was designed to answer the question: can I use the regime FOLFOX, which has become the standard treatment of metastatic colorectal cancer to achieve better outcomes in the earlier stages of the disease?
From October 1998 to January 2001 in 146 centers of 20 countries in the study were included in total, 2246 patients with stage II and III disease. After randomization of 1123 patients received treatment infusion 5-fluorouracil-leucovorin (scheme de Gramont), 1123-based combination regimens based on oxaliplatin (scheme FOLFOX4). The duration of therapy in both groups was 6 months. The primary endpoint in this study was a three-year disease-free survival, which is a predictor of five-year overall survival, but also directly reflects the effectiveness of therapy, whose aim is to prevent relapse.
Treatment resulted in a three-year survival rate of patients statistically significantly increased from 73 to 78%, and the risk of recurrence of the disease decreased by 23%.
The important thing is that the improvement of treatment results were achieved without compromising security. Adding to the treatment of oxaliplatin, 5-fluorouracil-leucovorin is not accompanied by a sharp increase in the frequency and severity of toxic effects. In favor of this demonstrated through the analysis of mortality (all deaths from any cause during the first month), which was one of the lowest among described in the literature (0.5%) in both treatment groups.
In 2007, the 43 th Congress of the American Society of Clinical Oncology (ASCO) have released the results of a six-year observation of patients. After using the scheme FOLFOX4 risk of death in patients with stage III colon cancer decreased by 20%.
Thus, the first time it was shown that compared with therapy 5-fluorouracil-leucovorin, combination therapy based on Eloksatina in cancer of the colon improves clinical outcomes at early stages of the disease. The data obtained allow to consider the regime FOLFOX4 as a new standard management of patients in this category. There is no doubt that in the next few years, treatment of early-stage colon cancer will be improved through the use of Eloksatina as the basis for adjuvant chemotherapy, as well as connecting agents with targeted action, the so-called Targeted Therapy (bevacizumab, tsetuksimab), and + development of new approaches to therapy Given the characteristics of the patient and the biological factors of prognosis.

- What are the current approaches in the treatment of unresectable cancers of the colon?
- In case of diagnosis of unresectable rectal cancer treatment strategy is an attempt to transfer tumor in rezektabelnuyu form, to achieve tumor regression through the use of radiation and chemotherapy.
Radiotherapy and chemotherapy can reduce the proliferative activity and is sufficient to reduce tumor size, which can perform a radical operation. In some studies provide data on fairly high numbers rezektabelnosti (40-90%) of tumor after chemo-radiation therapy using drugs such as capecitabine and oxaliplatin.
In some cases surgical removal of isolated metastases of colorectal cancer in the liver and lungs followed by chemotherapy, the five-year survival rate of patients in such cases, up to 40-50%.
If we estimate the overall survival of patients with stage IV colorectal cancer over the past few years, I noticed a definite improvement in treatment. The use of new drugs has increased the median overall survival of patients with 6-7 and 23 months only in the 1 st line therapy.