Second Opinion on Bowel cancer

Colorectal cancer (also "colorectal carcinoma", or “bowel cancer”) is a malignant transformation of cells in the colon (the longest part of the large intestine) or rectum (its last several inches). In the vast majority of cases those are the glandular cells of the mucous membranes and the disease is called adenocarcinoma; more rarely, other malignant masses, for example, neuroendocrine tumors or lymphomas, can also develop here.

How common is the disease?

Bowel cancer is number two by frequency in women (preceded by breast cancer) and number 3 in men (after prostate and lung malignancies). The median age of onset is over 70 years.

How is colorectal cancer diagnosed?

The diagnosis is made by a pathology lab specialist on the basis of microscopic examination of tumor tissue samples. They are usually obtained by removing a piece of the mass during a colonoscopy (endoscopic examination of the bowel).

Basic conclusions are drawn from the appearance: cancer cells look different from normal ones; there are also differences between various malignancy variations. In addition, certain "stains" with immune markers can be made (immunohistological testing). They make it possible to identify specific proteins that are present on the surface of cancer cells and are characteristic of a particular type of tumor. These findings confirm the initial diagnosis.

Furthermore, imaging is crucial when it comes to staging, i.e., determining the size of the tumor and its spread into other organs.

What are the bowel cancer subtypes?

A cancer consists of abnormal cells that proliferate and form a mass. In colorectal cancer, these are usually glandular cells in the intestinal mucosa that participate in the digestive process. Depending on where the growth starts, there are two main types: colon carcinoma (originating from the cells of the colon) and rectal carcinoma (originating from the rectum cells). The lesion location should be determined with great precision since it is decisive for therapy planning.

Tumors of the small intestine or anal canal are less common; these represent separate types and need a different treatment.

What is the role of DNA changes?

In addition to the histological (fine tissue) or immunohistological classification, molecular genetic testing also plays a role, as the genetic material of the tumor (DNA) can show very individual changes (mutations). These can strongly influence treatment.

Furthermore, in younger patients and in the presence of a family history of colorectal cancer, it is particularly important to look for defects in DNA damage response genes, since there are some hereditary disease types, for example, hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis (FAP).

Microsatellite instability testing is also part of genetic testing. Short gene segments with repeating sequences are examined for their length. Deviations are called microsatellite instability. This may indicate the possible mutations in the DNA damage response genes. In addition, tumors with microsatellite instability respond differently to certain therapies than microsatellite stable ones.

Another aim in genetic testing is the presence of the RAS and BRAF gene mutations, which will influence the choice of chemotherapy or antibody drugs.

What does the strategy depend on?

Basically, there are cancer-related as well as patient-related factors that determine treatment choice.

The cancer-related factors include its:

• type (by location and cell origin);
• grading (degree of aggressiveness)
• stage.

In addition to the above, the patient’s age, general health condition, medical history, as well as other individual features are also taken into consideration.

What are colon carcinoma treatment options and their goals?

Treatment modalities include surgery, radiation therapy, chemotherapy, and targeted cancer drugs, which can include both immunotherapy and specific antibodies.

• If the tumor is still in an early stage at the time of diagnosis, i.e., stage I, II or III, the goal is to cure the patient; this is referred to as curative care. The disease can be eliminated by complete surgical removal of the tumor. This is done by surgeons specialized in surgical procedures in the abdominal cavity.
• In many cases, drugs and or radiation are administered before and after surgery to shrink the mass and decrease the recurrence risks. The choice of these therapies depends on various factors such as the extent of the tumor, its nature, and lymph node involvement.
• If metastases are present (stage IV), when the tumor has spread to other parts of the body and no cure is longer possible, the aim is palliative. This means using therapies affecting the entire body, such as chemotherapy, in an attempt to halt tumor growth and maintain quality of life for as long as possible. In the case of colorectal cancer, there is one exclusion: if there are just a few metastases (e.g., only in the liver), they can also be removed by surgery. In this particular case, the goal is still curative.

What surgical procedures are available for the treatment of colorectal cancer?

The choice of surgical procedure is determined by the tumor size and location.

In the case of colon carcinoma, removal of the corresponding parts of the colon is performed depending on the location of the lesion.

In rectal cancer, a distinction is made between three surgical procedures depending on the height of the tumor.

Depending on the stage, regional connective tissue and regional lymph nodes are also removed (partial or total mesorectal excision).

Novel therapies for metastatic bowel cancer

If tumor removal is not possible, the highest priority is systemic management, i.e., measures effecting the entire body. Besides cytostatics, this also includes targeted medications such as immunotherapy and angiogenesis inhibitors (medications that stop the growth of tumor blood vessels). Besides, there are a number of state-of-the-art medications currently offered in clinical trials (e.g., cellular therapies / adoptive immunotherapies, targeted agents for specific mutations). Their choice is determined by certain histological and molecular genetic features of the tumor, including microsatellite stability or specific mutations.