Colorectal Cancer Treatments

Executive Summary

The different types of standard treatments for colorectal cancer are explained in detail. Standard treatments are used along with the integration of effective treatment planning. Clinical trials are used as an innovative treatment approach that combines different therapies and drugs for treating colorectal cancer. The standard treatments for colorectal cancer include surgery (laparoscopic surgery, colostomy for rectal cancer, and Radiofrequency ablation (RFA) / cryoablation), radiation therapy (external beam radiation therapy, stereotactic radiation therapy, intraoperative radiation therapy, brachytherapy), radiation therapy for rectal cancer ( neoadjuvant therapy, chemoradiation therapy), chemotherapy using standard treatment regimes using drugs, targeted therapy (anti-angiogenesis therapy, Epidermal growth factor receptor (EGFR) inhibitors, Combined targeted therapies, Tumour-agnostic treatment), and immunotherapy (Pembrolizumab, Nivolumab, Dostarlimab, Nivolumab and ipilimumab combination). Palliative care is provided to the patients to cope with mental, physical or financial issues while involving medication, nutritional changes, emotional and spiritual support and other relaxation therapies. Colorectal cancer treatment options by stage are also integrated, involving the polypectomy for stage 0, surgery for stage II, radiation therapy combined with chemotherapy for stage II rectal cancer, surgical removal of the tumor followed by adjuvant chemotherapy for stage III, and a combination of surgery, radiation therapy, targeted therapy, immunotherapy, and chemotherapy for stage IV colorectal cancer.

Treatment for Colorectal Cancer

“Standard to care” refers to the best-known treatment. In Colorectal cancer care, different doctors work together to bring out an overall Colorectal Cancer treatment plan for the patient. This is called a multidisciplinary team. 

Colorectal Cancer Treatments recommendations depend on many factors:

• The size, grade and type of tumor
• Whether the tumor is applying pressure on vital parts of the brain
• If the tumor has increased to other parts of the CNS or body
• Possible side effects
• The patient’s preferences and overall health

The standard treatments used for colorectal cancer are described below, followed by a brief outline of treatment options listed by stage ^​1​. 

Surgery for Colorectal Cancer

Surgery is the removal of the tumour and a few nearby healthy tissues during an operation. The purpose of surgery is to remove tissue to diagnose and remove the tumour to improve the prognosis. This Colorectal Cancer treatment is most common for colorectal cancer. A portion of the healthy colon or rectum and nearby lymph nodes will also be removed.

A colorectal surgeon is a doctor who received additional training to treat colon, rectum, and anus diseases. 

In addition to surgical resection, surgical alternatives for colorectal cancer include :

• Laparoscopic surgery – Some patients may have laparoscopic surgery for colorectal cancer ^​2​. In this technique, several viewing scopes are passed into the abdomen while a patient is under anesthesia. Anesthesia is a medicine that blocks the awareness of pain. The incisions are small, and the recovery time is often less than the standard colon surgery. Laparoscopic surgery is equally effective as conventional colon surgery in removing cancer. 
• Colostomy for rectal cancer –  Rarely, a person with rectal cancer may require a colostomy. This is a surgical opening or stoma through which the colon is connected to the abdominal surface to form a pathway for waste to be eliminated from the body. This waste gets collected in a pouch worn by the patient. Sometimes, the colostomy is temporary to allow the rectum to heal, but it can be permanent. With modern surgical techniques and radiation therapy and chemotherapy before surgery when needed, most people who receive treatment for rectal cancer don’t require a permanent colostomy. 
• Radiofrequency ablation (RFA) / cryoablation – Some patients may have surgery on the lungs or liver to remove tumors that have spread to those organs. Colorectal Cancer Optional treatments can be using energy in the form of radiofrequency waves to heat the tumors, known as RFA, or to freeze the tumor, called cryoablation. Not all liver or lung tumors can be treated with these approaches. RFA can be performed through the skin or during surgery. While this can help avoid removing parts of the lung and liver tissue that might be removed in regular surgery, there is also a chance that parts of the tumor will be left behind.

Generally, the side effects of surgery consist of pain and tenderness in the area of the operation. The operation may also cause constipation or diarrhoea, which usually disappears after a while. People who have a colostomy can have irritation around the stoma. If you need a colostomy, the doctor, nurse, or enterostomal therapist, a specialist in colostomy management, can teach you how to clean that area and prevent infection.

Many people learn to retrain their bowel after surgery. 

Radiation Therapy for Colorectal Cancer

Radiation therapy uses high-energy X-rays or particles to destroy cancer cells. It is generally used for treating rectal cancer because this kind of tumor tends to recur near where it originally started. A radiation therapy schedule consists typically of a specific number of treatments offered over a set period ^​3​.

• External beam radiation therapy – External-beam radiation therapy uses a machine to deliver x-rays to where the cancer is located. Radiation treatment is typically given five days a week for several weeks. It may be provided in the doctor’s office or at the hospital.
• Stereotactic Radiation Therapy – Stereotactic radiosurgery is a method to deliver high doses of radiation therapy directly to a tumour and not to healthy tissue. This technique can help save liver and lung tissue parts that might otherwise be removed during surgery. However, not all cancers that have grown and spread to the lung or liver can be treated in this way.
• Intraoperative Radiation therapy – This technique can help preserve parts of the liver and lung tissue that might otherwise have to be removed during surgery. However, not all cancers that have grown and spread to the lung or liver can be treated in this way.
• Brachytherapy – Brachytherapy uses radioactive ‘seeds’ placed inside the body. In a type of brachytherapy with a product known as SIR-Spheres, small amounts of a radioactive substance, yttrium-90, are injected into the liver to treat colorectal cancer that has spread to the liver when surgery is not an alternative. Limited information is available regarding how effective this approach is, but some studies suggest that it may help to slow down the growth of cancer cells.

Radiation therapy for Rectal cancer

Radiation therapy can be used before surgery for rectal cancer, called neoadjuvant therapy, to shrink the tumor, making it easier to remove. It can also be used post-surgery to destroy remaining cancer cells if any. Both approaches have worked to treat this disease. Chemotherapy is often given simultaneously as radiation therapy, known as chemoradiation therapy, to enhance the effectiveness of radiation therapy ^​4​.

Before surgery, chemotherapy therapy is used in rectal cancer to avoid colostomy or reduce cancer’s chance. One study showed that chemoradiation therapy before surgery was better and caused fewer side effects than radiation therapy and chemotherapy given post-surgery. The main benefits included a lower rate of cancer recurrence where it started, fewer patients who needed permanent colostomies, and some problems with scarring of the bowel where the radiation therapy was given.

Radiation therapy is typically given in the United States for rectal cancer over 5.5 weeks before surgery. However, for certain patients (in certain countries), a shorter course of 5 days of radiation therapy before surgery is appropriate or preferred.

A new approach to rectal cancer is currently being used for specific people. It is known as total neoadjuvant therapy (or TNT) ^​5​. With TNT, chemotherapy and chemoradiation therapy are given for around six months before surgery. This approach is still being studied to check which patients will benefit most.

Side effects from radiation therapy may include mild skin reactions, upset stomach, fatigue, and loose bowel movements. It may also cause bloody stools from bleeding through the rectum or blockage of the bowel. Most side effects go soon after treatment is completed.

Sexual problems and infertility (the inability to have a child) in both men and women may occur after the radiation therapy to the pelvis.

Chemotherapy for Colorectal Cancer

Chemotherapy uses medicine to kill or stop the growth of cancerous cells. Depending upon the stage, different chemotherapy is given. The point that makes a difference is how the chemotherapy enters the body and which cells it affects.

A chemotherapy schedule usually consists of a certain number of cycles over a fixed period. A patient can be given one drug at a time or a combination of different medications given simultaneously.

For some people having rectal cancer, the doctor will give chemotherapy and radiation therapy before the surgery to d the size of a rectal tumour and narrow the chance of cancer recurrence.

Many drugs are approved by the U.S. Food and Drug Administration to treat colorectal cancer in the United States ^​6​. The doctor may suggest one or more of them at different times during treatment. Sometimes these can be combined with targeted therapy drugs.

• Capecitabine (Xeloda)
• Fluorouracil (5-FU)
• Irinotecan (Camptosar)
• Oxaliplatin (Eloxatin)
• Trifluridine/tipiracil (Lonsurf)

Some standard treatment regimens using these drugs:

• 5-FU
• 5-FU with leucovorin (folinic acid), a vitamin that increases the effectiveness of 5-FU
• FOLFOX: 5-FU with leucovorin and oxaliplatin
• FOLFIRI: 5-FU with leucovorin and irinotecan
• Capecitabine, an oral form of 5-FU
• Irinotecan alone
• XELIRI/CAPIRI: Capecitabine with irinotecan
• XELOX/CAPEOX: Capecitabine with oxaliplatin
• Any of the above with one of the following targeted therapies: cetuximab (Erbitux), panitumumab (Vectibix) or bevacizumab (Avastin). Additionally, FOLFIRI may be combined with either of these targeted therapies: ziv-aflibercept (Zaltrap) or ramucirumab (Cyramza).

Chemotherapy may cause vomiting, nausea, diarrhoea, mouth sores, or neuropathy, numbness or tingling in feet or hands. But, medications to prevent these side effects are available. Because of the way drugs are given, these side effects are less severe than in the past for most people. In addition, patients may be exhausted, and there is an increased risk of infection. Significant hair loss is an unusual side effect with many drugs used to treat colorectal cancer, although it is more common with chemotherapy regimens that include irinotecan.

Targeted Therapy 

Targeted therapy aims at any factor contributing to the growth and development of cancer cells. It can be a specific protein, gene or tissue environment. These Colorectal Cancer treatments are typical and do not harm surrounding cells like those in chemotherapy or Radiotherapy ^​7​.

All tumors do not have the same target; doctors may recommend testing to understand better changes in the individual tumor’s genes and proteins. 

For colorectal cancer, the below-mentioned targeted therapies may be options.

Anti-angiogenesis therapy – Anti-angiogenesis therapy is focused on stopping angiogenesis, which forms blood vessels. Because a tumour requires the nutrients delivered by blood vessels to grow and then spread, anti-angiogenesis therapies aim to “starve” the tumour.

• Bevacizumab (Avastin) – When bevacizumab is given with chemotherapy, it increases the length of time people with advanced colorectal cancer live. In 2004, the FDA approved bevacizumab and chemotherapy as the first treatment, or first-line treatment, for advanced colorectal cancer. Recent studies showed it is also effective as second-line therapy and chemotherapy. There are two drugs similar to bevacizumab, bevacizumab-awwb (Mvasi) and bevacizumab-bvzr (Zirabev) that the FDA has also approved to treat advanced colorectal cancer. These are called biosimilars.
• Regorafenib (Stivarga) – This drug is used to treat people with metastatic colorectal cancer who have already received specific types of chemotherapy and other targeted therapies.
• Ziv-aflibercept (Zaltrap) and ramucirumab (Cyramza) – Either of these drugs can be combined with FOLFIRI chemotherapy as a second-line treatment for metastatic colorectal cancer.

Epidermal growth factor receptor (EGFR) inhibitors – Researchers have found that drugs that block EGFR may effectively stop or slow the growth of colorectal cancer.

• Cetuximab (Erbitux)
• Panitumumab (Vectibix)

Recent studies demonstrated that cetuximab and panitumumab do not work as well for tumours that have specific changes, called alterations or mutations, to a gene known as RAS. ASCO suggests that all people with metastatic colorectal cancer who may receive an EGFR inhibitor have their tumours tested for RAS and RAF gene mutations. If a tumour has a mutated form of the RAS gene or a specific BRAF mutation (V600E), ASCO recommends not receiving EGFR inhibitors.

Combined targeted therapies – Some tumours have a specific mutation, called BRAF V600E; an FDA-approved test can detect that. A class of targeted treatments known as BRAF inhibitors can treat tumours with this mutation. A combination using the cetuximab and BRAF inhibitor encorafenib (Braftovi) may be used to treat people having metastatic colorectal cancer with this mutation who have received at least one previous treatment.

Tumour-agnostic treatment – Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) are types of targeted therapy that are not specific to a particular type of cancer but focus on a specific genetic change known as an NTRK fusion. This kind of genetic change is rare but is found in a range of cancers, including colorectal cancer. These medications are approved as a treatment for metastatic colorectal cancer, cannot be removed with surgery, and have worsened with other treatments.

The tumour can also be tested for other molecular markers, like HER2 overexpression and others. These markers don’t have FDA-approved targeted therapies yet, but there may be opportunities in clinical trials studying these molecular changes.

The side effects of targeted treatments can be a rash on the face and upper body, reduced or prevented with various Colorectal Cancer treatments.

Immunotherapy 

Immunotherapy, also known as biologic therapy, is formed to boost the body’s natural defences to fight against cancer. It uses substances created by the body or in a laboratory to improve, target, or restore the functioning of the immune system.

Checkpoint inhibitors are an essential type of immunotherapy used to treat colorectal cancer ^​8​. 

• Pembrolizumab (Keytruda) – Pembrolizumab targets PD-1, a receptor on tumour cells, preventing the tumour cells from hiding from the immune system. Pembrolizumab is used to treat metastatic and unresectable colorectal cancers with a molecular feature known as microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). Unresectable means surgery is not an option.
• Nivolumab (Opdivo) – Nivolumab is used to treat people who are 12 or older and with MSI-H or dMMR metastatic colorectal cancer that has grown or spread post-treatment with chemotherapy with a fluoropyrimidine (like fluorouracil and capecitabine), oxaliplatin, and irinotecan.
• Dostarlimab (Jemperli) – Dostarlimab is a PD-1 immune checkpoint inhibitor. It can be used to treat metastatic or recurrent colorectal cancers with dMMR.
• Nivolumab and ipilimumab (Yervoy) combination – This checkpoint inhibitors combination is approved to treat patients who are 12 or older and with MSI-H, or dMMR metastatic colorectal cancer has grown or spread after treatment with chemotherapy with fluoropyrimidine, oxaliplatin, and irinotecan.

Different types of immunotherapy can cause various side effects. The common side effects of immunotherapy may include fatigue, rash, diarrhoea, nausea, fever, muscle pain, bone pain, itching, vomiting, joint pain, abdominal pain, shortness of breath, cough, and decreased appetite. Immunotherapy can increase the risk of inflammation in different organs in the body.

Palliative Care 

Colorectal Cancer and its treatments have side effects that can be mental, physical or financial and managing the effects are palliative or supportive care.

Palliative care includes medication, nutritional changes, emotional and spiritual support and other relaxation therapies. 

Palliative care focuses on alleviating how you feel during treatment by managing symptoms and supporting patients and their families with other non-medical needs. Regardless of type and stage of Cancer age, any person may receive this type of care.

Treatments by stage of Colorectal Cancer

Generally, stages 0, I, II, and III are primarily curable with surgery. However, people with stage III colorectal cancer, and few with stage II, receive chemotherapy after surgery to enhance the chance of eliminating the tumour. People with stage II and III rectal cancer receive radiation therapy with chemotherapy before or after surgery. Stage IV is often not curable, but it is treatable, and the growth of cancer and the symptoms of the disease can be regulated.

Stage 0 colorectal cancer

The standard Colorectal Cancer treatments is polypectomy, or the removal of a polyp, during a colonoscopy. No additional surgery is there unless the polyp can’t be entirely removed.

Stage I colorectal cancer

Surgical removal of the tumour and lymph nodes is usually the only treatment needed.

Stage II colorectal cancer

Surgery is usually the first treatment. People with stage II colorectal cancer should talk to their doctor if more treatment is needed post-surgery because, in some cases, adjuvant chemotherapy may be recommended. Adjuvant chemotherapy is a treatment after surgery to destroy any remaining cancer cells. However, cure rates for surgery alone are pretty good, and there are some benefits of additional treatment for patients with this stage of colorectal cancer. Talk to the doctors about the risks and benefits of adjuvant chemotherapy. A clinical trial can be an option after surgery.

Radiation therapy is typically combined with chemotherapy for stage II rectal cancer before or after surgery. Additional chemotherapy may be given after surgery as well.

Stage III colorectal cancer

Treatment commonly involves surgical removal of the tumour followed by adjuvant chemotherapy. A clinical trial can also be an option. Radiation therapy may be used alongside chemotherapy before or after surgery in rectal cancer, with adjuvant chemotherapy.

Metastatic (stage IV) colorectal cancer

If cancer spreads to a part of the body other than it initially started, it is called metastatic cancer. Colorectal cancer may spread to distant organs, like the lungs, liver, ovaries, and the tissue called the peritoneum that is linning of the abdomen. Doctors can have various opinions about the standard treatment plan. Clinical trials might be an option.

The Colorectal Cancer treatments plan can include a combination of surgery, radiation therapy, targeted therapy, immunotherapy, and chemotherapy, which can be used to restrict the spread of the disease and often temporarily shrink a cancerous tumour. Palliative care will also be essential to relieve side effects and symptoms.

At this stage, surgery to remove the part of the colon where cancer started usually cannot cure cancer. Still, it can help relieve a blockage of the colon or other problems associated with cancer. Surgery may be used to eliminate parts of other organs that contain cancer, known as resection, and can cure some patients if a limited amount of cancer spreads to a single organ, like the liver or a lung.

If colorectal cancer has proliferated to the liver only and the surgery is possible either before or after chemotherapy, there is a complete cure. Even if curing the cancer is not possible, surgery may add months or years to a person’s life. Deciding who can benefit from surgery for cancer that has spread to the liver is often complicated, involving multiple doctors working together to plan the best Colorectal Cancer treatments option.

Remission and chance of recurrence of Colorectal Cancer

When cancer can’t be detected in the body and there are no symptoms, this is known as remission. This may also be called having ‘no evidence of disease’ or ‘NED.’

A remission can be temporary or permanent. Many people worry about the recurrence of cancer.

The doctor performs another round of tests to know the extent of the recurrence.

Mainly the Colorectal Cancer treatments plan includes the treatments explained above, like surgery, chemotherapy, radiation therapy, and targeted therapy. 

If treatment doesn’t work

If cancer can’t be treated or controlled, it leads to advanced or terminal cancer. It is vital to have straightforward conversations with your health care team to express your feelings, preferences, and concerns. The health care team has unique skills, knowledge, and experience to assist patients and their families. Ensuring that a person is physically comfortable, free from pain, and emotionally supported is extremely important.