Colorectal cancer is a malignant tumor of the colon or rectum that can have many causes including genetic and environmental factors. It is one of the most common cancers worldwide with over 600,000 new cases detected each year. Diagnosis involves colonoscopy, biopsy, or imaging tests. Treatment may involve surgery to remove the tumor and affected tissues, radiation therapy to destroy cancer cells, and chemotherapy with drugs administered systemically to target cancer throughout the body. Outcomes depend on the stage of cancer, with early stage cancers having a better prognosis. Later stages indicate a larger tumor size, spread to lymph nodes or distant organs, and lower survival rates.

1. Colorectal cancer

2. A malignant neoplasm of the large intestine is a
malignant tumor of the colon and its appendage -
the appendage.
Due to the inaccurate translation of the English term
(eng. Colorectal cancer), often a generalized group
of such tumors is simply called colorectal cancer,
although in Russian it is a narrower term (not
including, in particular, colon lymphoma); the
English term also covers rectal cancer.

3. Epidemiology
Every year, according to E.S. Gruzdeva, more
than 600 thousand new cases of colon cancer
are detected in the world. In Russia, the
incidence is about 50 thousand new cases per
year. Not all cases of colorectal cancer are
detected even at a late stage, the figure is no
more than 70%.

4. Etiology
Colon cancer is a polyetiological disease, that is, it can have many causes. These
include: genetic factors, environmental factors (including nutrition, carcinogens),
inflammatory process in the intestine.
Although the genetics of colorectal cancer remain unexplained, recent studies show its
great importance in the development of the disease. Thus, a hereditary mutation in the
APC gene (eng.) Russian. is the cause of familial adenomatous polyposis, in which a
patient has an almost 100% chance of developing colon cancer by age 40 [1].
Two pathways can be traced in the occurrence of colorectal cancer: from ordinary
adenomas, starting with a mutation of the APC gene (Fearon-Vogelstein model) and
along the "jagged path", which is distinguished by a unique genetic profile and
morphological characteristics already at the initial stages of the development of
formations. Such formations occupy from 7-9%. The risk of developing cancer of
them is 7.5-15%. The precursors of epithelial formations are foci of aberrant crypts.

5. About 20% of colorectal cancers showed widespread defects in DNA methylation (the so-
called CIMP-positive profile), mutations in BRAF oncogenes (KRAS), microsatellite
instability, and many of them can arise within the dentate formations and determine their
morphological structure. Serrated polyposis syndrome also has specific genetic changes
associated with a biallelic mutation in the MUTYH gene. The risk of developing colorectal
cancer with this syndrome is very high and can be more than 50%, possibly the presence of
synchronous or metachronous cancers. They are usually accompanied by MSI-H and are
represented by a jagged morphology. Understanding the epigenetic pathway and molecular
characteristics of serrated lesions provides insight into their clinical relevance and provides
the evidence needed to treat and follow up patients with this disease.
Lynch syndrome (hereditary colon cancer without polyposis) is also associated with a high
risk of colon cancer before age 50. Unlike familial adenomatous polyposis, the proximal
colon is more likely to be affected with Lynch syndrome. Patients with this syndrome are
also at high risk of developing ovarian and uterine cancer at a young age. The syndrome is
caused by replication errors in the hMLH1, hMSH2, hMSH6, hPMS1, hPMS2 genes and,
possibly, other not yet known

6. Risk factors
Diet - eating foods that are poor in fiber and rich in
solid animal fats.
Drinking alcohol [5].
Obesity.
Smoking [6].
Inflammatory bowel disease.
Smokers with colon cancer have twice the risk of
dying compared to nonsmokers, according to a study
published in the Journal of Clinical Oncology.

7. Also, work was carried out, published in the journal Gut (The BMJ
journals), the results of which indicate that long-term use of antibiotics in
young and middle age increases the risk of colorectal adenomas prone to
malignancy [8]. Scientists investigated the relationship between long-term
antibiotic therapy (more than 2 months) at the age of 20-39 and 40-59
years with the development of adenomatous polyps. All participants
underwent a colonoscopy, which revealed that 1,195 of the 16,642
participants had colorectal adenomas. After analyzing the available data,
the researchers concluded that the use of antibiotics for more than 2
months in people aged 20-39 years leads to a 36% risk of polyp growth,
and at the age of 20-59 years - by 69%. The high risk of the transition of
adenoma to a malignant tumor has been confirmed by numerous studies.
The risk of developing cancer of the rectum and colon in people with
adenomatous polyps is 3-5 times higher than in the general population

8. Diagnostics
Colonoscopy with biopsy
Irrigoscopy
SCT of the pelvic organs, abdominal cavity

9. STAGES
The stage determines the location of the cancer, its spread, and the effect
on other organs and systems.
Stage information helps the doctor determine which
is optimal, and to predict the course of the disease.
There are several classifications of stages.
One of the methods for staging is the TNM system. Using the results of
diagnostic studies, the following tasks can be solved:
Tumor (T): how many layers has the neoplasm grown into the intestinal
wall.
Lymph nodes (N): has the tumor invaded the lymph nodes? If so, where
and to what extent.
Metastases (M): has the oncological process invaded other organs and
systems.

10. All results are combined for the final verdict.
There are 5 stages: stage 0 (zero) and stages I through IV (1 through 4). Determining
the stage will help describe the oncological process so that doctors jointly develop an
optimal treatment plan.
TNM system designations for bowel cancer:
Tumor (T)
In the TNM system, the letter T plus a letter or number (from 0 to 4) gives the answer to
how deep the neoplasm has grown into the intestinal mucosa. The stages are also
divided into small subgroups, which help to further characterize the tumor.
TX: Neoplasm is not assessed.
T0: No signs of bowel cancer.
Тis: carcinoma in situ. Malignant cells are detected only in the epithelial (upper) layer.
T1: The tumor has grown into the submucosa.
T2: The tumor has grown into the muscular layer of the intestine.
T3: The tumor has grown through the muscle layer and subserous. Or has grown into
tissues close to the intestines.
T4a: The tumor has grown through all layers of the intestine.
T4b: The tumor has grown or joined other adjacent organs.

11. Lymph node (N)
N in the TNM system - lymph nodes. These are small, bean-shaped organs found
throughout the body. Lymph nodes are part of the immune system. They help the
body fight off infections.
NX: Regional lymph nodes (RLNs) are not assessed.
N0: No propagation to RLU.
N1a: Malignant cells are detected in 1 RNU.
N1b: the process affects 2-3 lymph nodes.
N1c: Nodules of malignant cells form in the intestine.
N2a: oncological process captures 4-6 RLUs.
N2b: Malignant cells are found in 7 or more regional lymph nodes.
Metastases (M)
The "M" in TNM stands for the spread of cancer to neighboring organs. This is
called distant metastases.
M0: no metastases.
M1a: the oncological process has moved to 1 organ outside the intestine.
M1b: The tumor has grown to more than 1 organ excluding the intestine.
M1c: Cancer has invaded the entire surface of the peritoneum.
Grade of malignancy (G)

12. The grade describes how similar the cancerous cells are to healthy cells. If
a tumor resembles healthy tissue or includes groups of other cells, it is
called differentiated. If cancerous tissue is very different from healthy
tissue, it is called poorly differentiated. The degree of malignancy of a
disease will help determine how quickly it spreads. The lower the G
grade, the better the prognosis.
GX: tumor grade is undetectable.
G1: cells more like normal cells (well differentiated).
G2: cells similar to normal (moderately differentiated).
G3: cells have less in common with healthy cells (poorly differentiated).
G4: cells practically do not resemble healthy ones (undifferentiated).

13. Cancer grouping by stage
Stage 0: Also called carcinoma in situ. Tumor cells are found only in the mucous
membrane or the inner lining of the intestine.
Stage I: the oncological process has grown through the mucous membrane and
penetrated into the muscular layer of the intestine. It has not invaded nearby organs
or lymph nodes (T1 or T2, N0, M0).
Stage IIA: The tumor has grown through the wall of the colon or rectum, but has not
spread to adjacent organs and lymph nodes (T3, N0, M0).
Stage IIB: the oncological process has passed through the muscle layers to the
visceral peritoneum. It has not spread to nearby lymph nodes or anywhere else (T4a,
N0, M0).
Stage IIC: the formation has grown through all layers of the intestine, penetrating
into neighboring organs. It has not spread to the lymph nodes or anywhere else (T4b,
N0, M0).

14. Stage IIIA: The cancer has grown through several layers of the intestine. He moved to 1
-3 lymph nodes or tumor nodes in the intestinal tissues. Has not transferred to other
organs (T1 or T2, N1 or N1c, M0 or T1, N2a, M0).
Stage IIIB: The cancer has grown through the layers of the intestine or into surrounding
organs. Also in 1-3 lymph nodes or in the intestinal tumor node. It does not capture
adjacent organs (T3 or T4a, N1 or N1c, M0; T2 or T3, N2a, M0; or T1 or T2, N2b, M0).
Stage IIIC: Cancer has spread to 4 (or more) lymph nodes, but not to distant organs and
systems (T4a, N2a, M0; T3 or T4a, N2b, M0; or T4b, N1 or N2, M0).
Stage IVA: the tumor has spread to 1 distant organ (any T, any N, M1a).
Stage IVB: cancer has invaded 2 or more organs (any T, any N, M1b).
Stage IVC: the process has moved to the peritoneum. It can also capture other sites or
organs (any T, any N, M1c).

15. SYMPTOMS
The symptoms and signs of colorectal cancer listed in this
section overlap with symptoms of extremely common non-
cancerous conditions such as hemorrhoids and irritable bowel
syndrome. By paying attention to the symptoms of colorectal
cancer, it is possible to detect the disease at an early stage, when
it is successfully treated. However, many people with bowel
cancer do not develop symptoms until the disease progresses, so
people need to be screened regularly.
Colorectal cancer patients may experience the following
symptom complex:

16. Change in the frequency of bowel movements.
Diarrhea, constipation, or a feeling that the bowels are not emptying
completely.
Bright red or very dark blood in the stool.
Stool that looks narrower or thinner than usual.
Abdominal discomfort, including frequent gas pains, bloating, fullness,
and colic.
Weight loss for no reason.
Constant fatigue or malaise.
Unexplained iron deficiency anemia, that is, a decrease in the number of
red blood cells.
Talk to your doctor if any of these symptoms last for several weeks or get
worse.
Once cancer is diagnosed, symptom relief remains an important part of
cancer care and cancer treatment. This can be called palliative or
supportive care. It often begins shortly after diagnosis and continues
throughout treatment.

17. TREATMENT METHODS
“Standard of Care” refers to the best known
treatments. Clinical trials are testing a new
approach to treatment. Doctors want to know
if the new therapy is safer and more effective.
Clinical trials are an option for cancer care at all
stages of cancer.

18. Treatment overview
In cancer treatment, different doctors work together to develop an
overall plan for the patient's care. This is called an interdisciplinary
team. For colorectal cancer, these teams may include a surgeon,
chemotherapist, radiologist, and gastroenterologist. A gastroenterologist
is a doctor who specializes in the gastrointestinal tract.
For treatment to be suitable for every patient, all decisions must be made
taking into account factors such as:
Concomitant chronic pathology.
The general health of the patient.
Potential side effects of the treatment plan.
Other medications the patient is already taking.
Nutritional status and social support of the patient.

19. Surgical intervention
This is the elimination of the neoplasm and surrounding healthy
tissue with the help of surgery. It is the most current treatment for
colorectal cancer. A portion of the healthy colon or rectum and
adjacent lymph nodes are also removed. An oncologist surgeon is
a doctor who specializes in the treatment of cancer with surgical
methods. A colorectal surgeon is a physician who has received
additional training to treat diseases of the colon, rectum, and
anus. Colorectal surgeons used to be called proctologists.
In addition to resection, surgical options for colorectal cancer
include:

20. -Laparoscopic surgery. With this technique, multiple visual guides are inserted into the abdominal
cavity while the patient is under anesthesia. At the same time, both incisions and recovery times are
shorter than with standard colon surgery.
-Colostomy for rectal cancer. A colostomy is a surgical opening through which the large intestine
connects to the abdominal surface to provide a pathway for processed food to exit the body. This
processed food is collected in a bag that the patient carries. Sometimes a colostomy is only temporary
while the rectum heals, but it may be permanent. Thanks to modern surgical methods of radiation
therapy and chemotherapy before surgery, most people with rectal cancer do not need a permanent
colostomy.
-Radiofrequency ablation (RA) or cryoablation. Some patients may require liver or lung surgery to
remove tumors that have spread to these organs. Energy is used in the form of radio frequency waves
to heat tumors (RA), or to freeze tumors - cryoablation. RA can be done through the skin or by
surgery. This will help to avoid removing some of the liver and lung tissue that would have to be
removed in a normal operation. However, there is also the possibility that parts of the tumor may
remain.
Side effects of surgery
The surgery can cause constipation or diarrhea, which usually go away after a while. People with
colostomy may experience irritation around the stoma. If you need a colostomy, your doctor, nurse, or
enterostomy therapist can teach you how to cleanse the area and prevent infection.

21. Radiation therapy
It is the use of high-energy X-rays to destroy
malignant cells. This method is commonly
used to treat rectal cancer because this
tumor tends to recur near where it originally
appeared. A radiation therapist is called a
radiologist. A radiation therapy regimen, or
regimen, usually consists of repeated
treatments over a period of time.

22. -External beam radiation therapy. With external external beam radiation therapy, an apparatus
is used to deliver radiation to the malignant focus. Radiation therapy is usually given 5 days a
week for several weeks.
-Stereotactic radiation therapy. This is a type of external beam radiation therapy that is used
when a tumor has spread to the liver or lungs. With this treatment option, a concentrated dose
of radiation is delivered to a small area. The technique helps preserve parts of the liver and
lung tissue that might otherwise have been removed during surgery.
Intraoperative radiation therapy. One high dose of radiation therapy is given during surgery.
-Brachytherapy. The use of radioactive "seeds" that are placed inside the body. In Type 1
brachytherapy, using a device called SIR spheres, tiny amounts of a radioactive substance
called yttrium-90 are injected into the liver. Used to treat colorectal cancer that has spread to
the liver when surgery is not possible.
-Chemotherapy is often given in combination with radiation therapy for greater effectiveness.
This is called chemoradiotherapy.
The main advantages of this method are a decrease in the incidence of cancer in the original
area, a decrease in the number of patients who require permanent colostomy, and a decrease
in problems with intestinal scarring in the place where radiation therapy was performed.

23. Side effects of radiation therapy
Adverse effects of radiation therapy may include
fatigue, mild skin manifestations, and dyspepsia.
The method can also cause blood to appear in the
stool due to rectal bleeding or a blockage in the
intestines. The negative consequences disappear
after the end of treatment.
Sexual problems, as well as infertility in both men
and women, can occur after pelvic radiation
therapy.

24. Drug therapy
Systemic therapy is the use of medications to eliminate tumor cells.
These drugs are injected through the bloodstream to reach cancer cells
throughout the body.
Systemic treatment includes placing an intravenous (IV) catheter into a
vein with a needle or swallowing (oral) tablets.
For colorectal cancer, the following types of systemic therapy are used:
Chemotherapy
Targeted therapy
Immunotherapy
The patient can receive both one and several types at the same time.

25. Chemotherapy
This is the use of drugs that destroy tumor cells, preventing them from
growing, dividing and producing new cells.
The treatment regimen most often consists of several cycles of procedures. At
the same time, the patient can receive 1 drug or a combination of different
drugs.
Chemotherapy may be given after surgery to eliminate any remaining cancer
cells. For some patients with rectal cancer, doctors prescribe
chemoradiotherapy to shrink the tumor before surgery. Treatment minimizes
the likelihood of relapse.
Side effects of chemotherapy
Chemotherapy can cause dyspepsia, neuropathy, or mouth sores. However,
medications are available to prevent these side effects. Neuropathy, which is
tingling or numbness in the legs or arms, can also occur after certain
medications. Significant hair loss is a rare side effect

26. Targeted therapy
Oncology treatment option. Affects specific genes, the proteinaceous
environment of cancer, blocking the growth and division of malignant cells.
Healthy cells are not damaged in this case. Scientists have shown that
targeted therapy helps older patients as much as younger patients.
The following targeted therapy is used in the treatment of colorectal cancer:
-Antiangiogenic therapy. It inhibits the process of the appearance of new
arteries and veins. For the development of a tumor, nutrients supplied
through the blood vessels are needed, so the goal of anti-angiogenic therapy
is to “deplete” the tumor.
-Bevacizumab. Restrains the development of the oncological process.
Regorafenib. It has proven itself in the metastatic process.
Ziv-aflibercept and ramucirumab. Any of these drugs can be combined with
chemotherapy.

27. -Epidermal growth factor receptor (EGFR) inhibitors. They stop or slow down the
development of the oncological process.
Cetuximab (Erbitux). Cetuximab is an antibody derived from mouse cells.
Panitumumab (Vectibix). Made entirely from human proteins. Less allergenic. Recent
studies show that cetuximab and panitumumab also do not work for tumors that have
specific mutations or changes in a gene called RAS.
-Agnostic anticancer therapy. Larotrectinib (Vitrakvi) is a targeted therapy that is not
specific to a particular type of cancer, but focuses on specific genetic changes in the
NTRK genes.
The tumor can also be tested for other molecular markers, including BRAF, HER2
overexpression, and others. There is no FDA-approved targeted therapy for these
markers yet, but there are prospects associated with clinical trials that study these
molecular changes.
Side effects of targeted therapy
May include a rash on the face and upper body, which can be prevented or reduced with
a variety of treatments.

28. Immunotherapy
An alternative name is biological therapy. Helps to enhance the body's immune
response in cancer. It uses substances produced by the body or produced in a
laboratory to improve the functioning of the immune system.
Checkpoint inhibitors are an important immunotherapy used to treat colorectal
cancer.
Pembrolizumab. Recommended for metastatic colorectal cancer with
characteristic microsatellite instability (MSI-H) or deficiency in replication error
repair (dMMR).
Nivolumab. Used to treat patients with metastatic colorectal cancer with MSI-H
or dMMR that has increased or spread after chemotherapy with fluoropyrimidine
(such as capecitabine and fluorouracil), oxaliplatin, and irinotecan.
Nivolumab and ipilimumab. This combination of checkpoint inhibitors is
approved for the treatment of metastatic colorectal cancer patients with MSI-H or
dMMR.

29. Side effects of immunotherapy
The most common negative effects of treatment are
fatigue, dermatitis, fever, muscle pain, bone pain,
dyspepsia, cough, shortness of breath.
Cancer and cancer treatments cause physical
symptoms and side effects, as well as psychological,
social and financial consequences. Managing all of
these effects is called palliative (supportive) therapy.

30. Treatment options for different stages of the disease
Stages 0, I, II, and III are often curable with surgery. Moreover, many patients
with stage III and sometimes stage II colorectal cancer receive chemotherapy
after surgery to increase the likelihood of complete elimination of the pathology.
People with stage II and III rectal cancer also receive radiation therapy with
chemotherapy before or after surgery.
Stage 0 colorectal cancer
The usual treatment is polypectomy, or removal of the polyp during colonoscopy.
Additional surgery is not performed, unless the polyp is not completely removed.
Colorectal cancer stage I
Excision of the tumor and lymph nodes is most often the only treatment needed.

31. Colorectal cancer stage II
Surgery is the initial treatment. Adjuvant therapy is also possible.
This is a type of treatment given after surgery to kill any remaining
cancer cells. Although the cure rates for surgery are quite high, there
are several benefits of complementary treatment for people with this
stage of colorectal cancer.
Colorectal cancer stage III
Treatment consists of surgery followed by adjuvant chemotherapy.
You can also consider clinical trials. For rectal cancer, radiotherapy is
used with chemotherapy before or after surgery, along with adjuvant
chemotherapy.

32. Metastatic (stage IV) colorectal cancer
If the oncology spreads to another organ, doctors call it metastatic. Colon cancer can
spread to distant organs (ovaries, pulmonary system, liver).
Treatment consists of a combined action of surgery, radiotherapy, immunotherapy
and chemotherapy. They are used to slow the spread of the disease and often to
temporarily shrink a cancerous tumor. Palliative care is also important.
At this stage, surgery to remove part of the colon usually cannot cure the cancer, but
it can help clear a blockage in the colon or other problems associated with the
disease. Surgery (resection) can also be used to remove parts of other organs.
Resection helps some patients if a limited number of cancer cells have spread to a
single organ, such as the liver or lung.
If colorectal cancer has spread only to the liver and if surgery is possible - before or
after chemotherapy - there is a chance of a complete cure. Even when cancer cannot
be cured, surgery can add months or even years to your life.

33. RISK FACTORS AND PREVENTION
A risk factor is anything that increases the likelihood of developing an
oncological process. Knowing your risk factors and discussing them with your
doctor can help you make more informed lifestyle and health care choices.
A person with moderate levels of factors is about 5% more likely to develop
bowel cancer. Typically, most cases of colorectal cancer (about 95%) are
considered sporadic, meaning that genetic changes develop randomly after a
person is born, so there is no risk of passing these genetic changes to children.
The hereditary form is less common (about 5%) and occurs when gene
mutations or changes are passed from one generation to the next.
The following factors increase the likelihood of a person developing bowel
cancer:

34. Age. The risk of colorectal cancer increases with age. Colorectal cancer can
occur in young people and adolescents, but most cases of colorectal cancer
occur in people over the age of 50. For colon cancer, the median age at
diagnosis is 68 for men and 72 for women. For rectal cancer, this is 63
years for both men and women.
Floor. Men have a slightly higher risk of developing colorectal cancer than
women.
Family history of colorectal cancer. Colorectal cancer can be considered
familial if first-degree relatives (parents, siblings, children) or many other
family members (grandparents, aunts, uncles, nieces, nephews,
grandchildren, cousins) have been diagnosed with a similar diagnosis.

35. Rare hereditary diseases. Family members with rare hereditary diseases
also have a high risk of developing cancer. Among them:
Familial adenomatous polyposis (FAP)
Attenuated familial adenomatous polyposis (AFAP), FAP subtype
Gardner's syndrome, subtype FAP
Juvenile polyposis syndrome
Lynch syndrome, also called hereditary non-polyposis colorectal cancer
Muir-Torre syndrome, a subtype of Lynch syndrome
MYH-associated polyposis
Petz-Yegers syndrome
Turco syndrome, subtype of FAP and Lynch syndrome
Inflammatory bowel disease (IBD). People with IBD (ulcerative colitis,
Crohn's disease) can develop chronic inflammation of the colon. This
increases the risk of bowel cancer.

36. Adenomatous polyps. Some types of polyps, called adenomas, can develop into
colorectal cancer over time. Often times, polyps can be completely removed
with a special instrument during a colonoscopy. This is a study in which a
doctor examines the colon with an illuminated tube after sedating a patient.
Removing polyps can prevent colorectal cancer. People who have had
adenomas are at greater risk of additional polyps and colorectal cancer and
should have regular follow-up screening tests.
Some types of cancer in history. Women who have had ovarian or uterine cancer
are more likely to develop colorectal cancer.
Racial affiliation. Blacks have the highest rates of sporadic colorectal cancer.
Physical inactivity and obesity. People who lead a sedentary lifestyle, as well as
people who are overweight or obese, are at risk.
Food. Modern research has consistently linked the consumption of large
amounts of protein foods (red meat) with a high risk of disease.
Smoking. Smokers are more likely to die from colorectal cancer than non-
smokers.