Colon cancer

What is this ?

Colon and rectal cancers affected approximately 1.93 million people worldwide in 2020, according to estimates from the International Agency for Research on Cancer (IARC). This makes them the third most diagnosed cancers globally, after lung and breast cancers. These cancers are more common in men than in women.

The average lifetime risk of developing colorectal cancer is estimated to be between 3% and 5% worldwide. This risk increases with age, particularly after 40, with the majority of cases occurring in individuals aged 50 and older. The average age at diagnosis is estimated to be over 70 for both sexes.

Colorectal cancer caused approximately 935,000 deaths in 2020, accounting for 9.4% of all cancer deaths worldwide, making it the second leading cause of cancer-related mortality after lung cancer (World Health Organization (WHO) and The Cancer Atlas).

Colorectal cancer primarily manifests as adenocarcinomas (malignant tumors) that develop from the cells of the colonic mucosa. The disease is defined by its location (right colon, left colon, rectum), which influences treatment approaches, and by the molecular status of the tumor.

Interview with Professor Romain Coriat

Risk factors for colon cancer

Colon cancer has a multifactorial origin: heredity, lifestyle, and exposure to substances that promote cancer occurrence.

Patients are classified into 3 groups :

• Individuals at average risk : aged over 50, who are offered national screening for blood in the stool.
• Individuals at high risk of colorectal cancer: history of polyps, colon cancer, or a parent diagnosed with colorectal cancer before 65, or chronic inflammatory bowel disease.
• Individuals at very high risk of colorectal cancer: carriers of genetic conditions predisposing them to colon cancer.

The latter two categories require specialized surveillance by a gastroenterologist.

Currently, routine molecular abnormalities investigated include :

• Detection of microsatellite instability, which helps select patients benefiting from immunotherapy.
• Mutation testing of RAS genes, which contraindicates anti-EGFR targeted therapies (ineffective for these conditions).
• BRAF gene mutation testing, which guides treatment with targeted therapies aimed at the BRAF gene.

Sometimes an MRI of the rectum or a PET scan may be requested.

Screening

Today, there is a nationwide organized screening program that involves testing for blood in the stool, offered every 2 years starting at age 50.

Symptoms

The most common symptoms of colon cancer involve both bowel movement issues and unexplained deterioration in the patient's overall condition.

Symptoms may include :

• Abdominal pain
• Digestive obstruction: cessation of gas and bowel movements with vomiting.
• Transit disorders with alternation of diarrhea-constipation
• Presence of blood in the stool
• Unusual and persistent fatigue
• Unexplained weight loss
• Loss of appetite
• Blood tests revealing anemia

Diagnosis

Le diagnostic du cancer du côlon repose sur une coloscopie réalisée le plus souvent sous anesthésie générale.

It confirms the presence of a tumor, its location, and involves taking a histological sample (confirming the cancer diagnosis).

For a comprehensive diagnosis, the cancer's characteristics are determined through various examinations :

• Staging with imaging: including a thorax, abdomen, and pelvis CT scan. Sometimes an MRI of the rectum or a PET scan may be requested.
• Histological diagnosis: following a biopsy typically conducted during colonoscopy. An anatomopathologist then analyzes the tissues to define the cancer type, histological subtype, and identifies markers to tailor the treatment.
• Molecular analysis: to identify potential predictive mutations such as the RAS gene implicated in the development of these cancers.

Treatments

The treatment of colorectal cancer is primarily linked to the stage and molecular characteristics of the tumors.

Localized colon tumors are typically managed with surgical intervention aimed at removing the tumor. In some cases, this surgery is followed by post-operative chemotherapy, known as "adjuvant" chemotherapy.

For localized rectal cancers, treatment involves radiotherapy alone or combined with chemotherapy before surgery, in a "neoadjuvant" setting.

Therapeutic strategies for metastatic cancers are more complex.

They may involve surgery for the primary tumor and metastases, followed by chemotherapy.

However, treatment primarily relies on medical therapies including intravenous or oral chemotherapy, targeted therapies tailored to the genetic characteristics of the tumor.

Additionally, a small subset of patients may benefit from immunotherapy using anti-PD-1 (checkpoint inhibitor) therapies, often yielding remarkable results.