Stage IV Colorectal Cancer

Treatment for stage 4 colon cancer or stage 4 rectal cancer is complex, and generally requires
consultation with medical, surgical, and radiation oncology specialists. This cancer is
considered metastatic colorectal cancer.

Stage IV Colorectal Cancer

Treatment for stage 4 colon cancer or stage 4 rectal cancer is complex, and generally requires consultation with medical, surgical, and radiation oncology specialists. This cancer is considered metastatic colorectal cancer.

Your treatment will be specialized depending on your specific circumstances, which include the organs your cancer has spread to, which biomarkers your cancer possesses, and what therapies you have already tried.

Take time to get the best information and advice possible from a multidisciplinary team. This process is vitally important. Make sure to get a second opinion, even if it takes extra time.

Your treatment will be specialized depending on your specific circumstances, which include the organs your cancer has spread to, which biomarkers your cancer possesses, and what therapies you have already tried.

Take time to get the best information and advice possible from a multidisciplinary team. This process is vitally important. Make sure to get a second opinion, even if it takes extra time.

Biomarker testing

All colorectal cancer stage 4 patients should undergo biomarker testing. Biomarkers are targetable features of a cancer, often mutations or changes in specific genes that can be targeted by specific drugs or therapies. Biomarker testing can give your treatment team a better idea of which therapies might work, and which therapies they should avoid.

All metastatic colorectal cancers should be tested for the following biomarkers at a minimum:

  • Mismatch repair deficiency or microsatellite instability (dMMR/MSI-H)
  • RAS mutations (KRAS or NRAS)
  • BRAF mutations
  • HER2 amplification

It is possible to test for many biomarkers at one time using a process called next generation sequencing (NGS). NGS can find some rare biomarkers that may have specific treatments available, such as:

  • POLE/POLD1 mutations
  • RET fusions
  • NTRK fusions
  • DPD deficiency testing, if receiving 5-FU or capecitabine

Biomarker testing

Treatment for stage 4 colon cancer or stage 4 rectal cancer is complex should undergo biomarker testing. Biomarkers are targetable features of a cancer, often mutations or changes in specific genes that can be targeted by specific drugs or therapies. Biomarker testing can give your treatment team a better idea of which therapies might work, and which therapies they should avoid.

All metastatic colorectal cancers should be tested for the following biomarkers at a minimum:

  • Mismatch repair deficiency or microsatellite instability (dMMR/MSI-H)
  • RAS mutations (KRAS or NRAS)
  • BRAF mutations
  • HER2 amplification

It is possible to test for many biomarkers at one time using a process called next generation sequencing (NGS). NGS can find some rare biomarkers that may have specific treatments available, such as:

  • POLE/POLD1 mutations
  • RET fusions
  • NTRK fusions
  • DPD deficiency testing, if receiving 5-FU or capecitabine

Surgery

If the liver, lungs, or the lining of the abdomen (peritoneum) are affected, you may undergo multiple surgeries to remove metastatic disease. Often, chemotherapy and radiation are combined with surgery to shrink tumors.

is also known as a liver resection, This surgery is intended to remove tumors from the liver.
is a surgery where tumors, which have metastasized to the lung, are removed.
is also called HIPEC. This surgery involves filling the abdominal cavity with heated chemotherapy drugs.
is used in specialized cases, with or without HIPEC. Cytoreductive surgery aims to surgically remove all visible tumors in the abdomen.

Surgery

If the liver, lungs, or the lining of the abdomen (peritoneum) are affected, you may undergo multiple surgeries to remove metastatic disease. Often, chemotherapy and radiation are combined with surgery to shrink tumors.

is also known as a liver resection, This surgery is intended to remove tumors from the liver.
is a surgery where tumors, which have metastasized to the lung, are removed.
is also called HIPEC. This surgery involves filling the abdominal cavity with heated chemotherapy drugs.
is used in specialized cases, with or without HIPEC. Cytoreductive surgery aims to surgically remove all visible tumors in the abdomen.

Interventional radiology procedures

Ablation and chemoembolization are advanced interventional radiology techniques used to target and treat tumors.

  • Ablation: is used to destroy small tumors on the liver or lungs. Ablation involves guiding a specialized needle or probe into or near the tumor and delivering targeted energy to the tumor, hopefully destroying it while avoiding damaging the surrounding tissues. Ablation may also be performed using targeted radiation, referred to as “ablative radiotherapy.”
  • Chemoembolization: is sometimes called transarterial chemoembolization (TACE). It is a combination of an embolization procedure (a procedure that reduces blood flow to the liver) and chemotherapy.

Radiation therapy

Two advanced radiation therapy techniques used to treat colorectal cancer are:

  • Stereotactic body radiation therapy (SBRT): is where high doses of radiation are directed at tumors in the body using very precise beams by an external machine. SBRT may be used to treat colorectal cancer that has spread to the lungs, liver, or bones.
  • Selective internal radiation therapy (SIRT): is a procedure that delivers tiny radioactive beads directly to the tumor(s) in the liver. The beads are injected into blood vessels leading to the tumor, causing them to collect in the tumor and deliver radiation.

Interventional radiology procedures

Ablation and chemoembolization are advanced interventional radiology techniques used to target and treat tumors.

  • Ablation: is used to destroy small tumors on the liver or lungs. Ablation involves guiding a specialized needle or probe into or near the tumor and delivering targeted energy to the tumor, hopefully destroying it while avoiding damaging the surrounding tissues. Ablation may also be performed using targeted radiation, referred to as “ablative radiotherapy.”
  • Chemoembolization: is sometimes called transarterial chemoembolization (TACE). It is a combination of an embolization procedure (a procedure that reduces blood flow to the liver) and chemotherapy.

Radiation therapy

Two advanced radiation therapy techniques used to treat colorectal cancer are:

  • Stereotactic body radiation therapy (SBRT): is where high doses of radiation are directed at tumors in the body using very precise beams by an external machine. SBRT may be used to treat colorectal cancer that has spread to the lungs, liver, or bones.
  • Selective internal radiation therapy (SIRT): is a procedure that delivers tiny radioactive beads directly to the tumor(s) in the liver. The beads are injected into blood vessels leading to the tumor, causing them to collect in the tumor and deliver radiation.

Chemotherapy combinations

There are a variety of chemotherapy combinations that may be prescribed.

CapeOx or Xelox

capecitabine (Xeloda®) plus oxaliplatin (Eloxatin®). Capecitabine is an oral drug that works the same way as 5-FU inside the cancer cell.

Folfox

5-FU, irinotecan (Camptosar®), and leucovorin

These regimens may be combined with targeted therapies such as bevacizumab (Avastin®), cetuximab (Erbitux®), or panitumumab (Vectibix®).

Folfiri

5-FU, irinotecan (Camptosar®), and leucovorin

These regimens may be combined with targeted therapies such as bevacizumab (Avastin®), cetuximab (Erbitux®), or panitumumab (Vectibix®).

Folfirinox

includes leucovorin, 5-FU, irinotecan, and oxaliplatin. This may also be combined with the targeted therapy bevacizumab (Avastin®)

Patients who are not able to tolerate intensive therapy have other options. Doctors may recommend:

  • 5-FU plus leucovorin with or without bevacizumab (Avastin®)
  • Capecitabine (Xeloda®) with or without bevacizumab (Avastin®) – treatment with capecitabine (Xeloda®) alone should only be considered a reasonable option for selected patients who are not candidates for more aggressive combination regimens with oxaliplatin (Eloxatin®) or irinotecan (Camptosar®).

Other options

Trifluridine and tipiracil (Lonsurf®)

Lonsurf is an oral therapy that may be used in metastatic (stage IV) colorectal cancer, with or without bevacizumab.

Chemotherapy combinations

There are a variety of chemotherapy combinations that may be prescribed.

CapeOx or Xelox

capecitabine (Xeloda®) plus oxaliplatin (Eloxatin®). Capecitabine is an oral drug that works the same way as 5-FU inside the cancer cell.

Folfox

5-FU, irinotecan (Camptosar®), and leucovorin

These regimens may be combined with targeted therapies such as bevacizumab (Avastin®), cetuximab (Erbitux®), or panitumumab (Vectibix®).

Folfiri

5-FU, irinotecan (Camptosar®), and leucovorin

These regimens may be combined with targeted therapies such as bevacizumab (Avastin®), cetuximab (Erbitux®), or panitumumab (Vectibix®).

Folfirinox

includes leucovorin, 5-FU, irinotecan, and oxaliplatin. This may also be combined with the targeted therapy bevacizumab (Avastin®)

Patients who are not able to tolerate intensive therapy have other options. Doctors may recommend:

  • 5-FU plus leucovorin with or without bevacizumab (Avastin®)
  • Capecitabine (Xeloda®) with or without bevacizumab (Avastin®) – treatment with capecitabine (Xeloda®) alone should only be considered a reasonable option for selected patients who are not candidates for more aggressive combination regimens with oxaliplatin (Eloxatin®) or irinotecan (Camptosar®).

Other options

Trifluridine and tipiracil (Lonsurf®)

Lonsurf is an oral therapy that may be used in metastatic (stage IV) colorectal cancer, with or without bevacizumab.

Targeted therapies

Targeted therapies are not chemotherapy, and work in different ways. They may work when chemotherapy doesn’t and may present different side effects. Targeted therapies may be used alone, with chemotherapy, or in combination with other targeted therapies. There are approved targeted therapies for colorectal cancer, including:

Used in patients whose cancer has the EGFR gene and the wild-type KRAS gene. May also be used in patients whose cancer has certain BRAF mutations

May be used with FOLFOX as a first-line therapy in patients whose cancer does not have a mutation in any of the RAS genes.

May be used with 5-FU as a first or second treatment, or with a fluoropyrimidine and either irinotecan hydrochloride or oxaliplatin as the second treatment in patients whose disease has gotten worse after therapy that included bevacizumab.

Used in stage IV cancer with FOLFIRI in patients whose disease has not gotten better with other chemotherapy.

Approved to treat stage IV cancer in patients who have not gotten better with other treatments.

Approved for use in stage IV cancer with FOLFIRI in patients whose disease has gotten worse during or after treatment with bevacizumab, oxaliplatin, and a fluoropyrimidine.

Approved for use in patients whose cancer has a certain mutation in the BRAF gene.

Used in stage IV cancer in patients who have received previous treatment with a fluoropyrimidine, oxaliplatin, irinotecan hydrochloride, and an anti-VEGF therapy. If a patients cancer has the wild-type KRAS gene, that patient may have also received an anti-EGFR therapy.

Used in stage IV cancer with cetuximab in patients who have received previous treatment.

Approved as a first-line treatment in combination with cetuximab, 5-FU, leucovorin, and oxaliplatin in patients with metastatic colorectal cancer and a BRAF V600E mutation.

Used in HER2 positive cancer in combination with pertuzumab, lapatinib, or tucatinib.

Used in HER2 positive cancer in combination with trastuzumab.

For use in colorectal cancer that cannot be removed surgically or has spread to other parts of the body and has the wild-type RAS gene. Used with trastuzumab in patients who have received treatment with a fluoropyrimidine, oxaliplatin, and irinotecan hydrochloride and it did not work or is no longer working.

Used in HER2 positive cancer in combination with trastuzumab.

Used in HER2 positive cancer.

Used in stage IV tumors that have an NTRK gene fusion.

Used in stage IV tumors that have an NTRK gene fusion.

Used in stage IV cancers that have a RET gene fusion.

Used in cancers with a KRAS G12C mutation in combination with cetuximab or panitumumab.

Used in cancers with a KRAS G12C mutation in combination with cetuximab or panitumumab.

Targeted therapies

Targeted therapies are not chemotherapy, and work in different ways. They may work when chemotherapy doesn’t and may present different side effects. Targeted therapies may be used alone, with chemotherapy, or in combination with other targeted therapies. There are approved targeted therapies for colorectal cancer, including:

Used in patients whose cancer has the EGFR gene and the wild-type KRAS gene. May also be used in patients whose cancer has certain BRAF mutations

May be used with FOLFOX as a first-line therapy in patients whose cancer does not have a mutation in any of the RAS genes.

May be used with 5-FU as a first or second treatment, or with a fluoropyrimidine and either irinotecan hydrochloride or oxaliplatin as the second treatment in patients whose disease has gotten worse after therapy that included bevacizumab.

Used in stage IV cancer with FOLFIRI in patients whose disease has not gotten better with other chemotherapy.

Approved to treat stage IV cancer in patients who have not gotten better with other treatments.

Approved for use in stage IV cancer with FOLFIRI in patients whose disease has gotten worse during or after treatment with bevacizumab, oxaliplatin, and a fluoropyrimidine.

Approved for use in patients whose cancer has a certain mutation in the BRAF gene.

Used in stage IV cancer in patients who have received previous treatment with a fluoropyrimidine, oxaliplatin, irinotecan hydrochloride, and an anti-VEGF therapy. If a patients cancer has the wild-type KRAS gene, that patient may have also received an anti-EGFR therapy.

Used in stage IV cancer with cetuximab in patients who have received previous treatment.

Approved as a first-line treatment in combination with cetuximab, 5-FU, leucovorin, and oxaliplatin in patients with metastatic colorectal cancer and a BRAF V600E mutation.

Used in HER2 positive cancer in combination with pertuzumab, lapatinib, or tucatinib.

Used in HER2 positive cancer in combination with trastuzumab.

For use in colorectal cancer that cannot be removed surgically or has spread to other parts of the body and has the wild-type RAS gene. Used with trastuzumab in patients who have received treatment with a fluoropyrimidine, oxaliplatin, and irinotecan hydrochloride and it did not work or is no longer working.

Used in HER2 positive cancer in combination with trastuzumab.

Used in HER2 positive cancer.

Used in stage IV tumors that have an NTRK gene fusion.

Used in stage IV tumors that have an NTRK gene fusion.

Used in stage IV cancers that have a RET gene fusion.

Used in cancers with a KRAS G12C mutation in combination with cetuximab or panitumumab.

Used in cancers with a KRAS G12C mutation in combination with cetuximab or panitumumab.

Immunotherapies

Immunotherapy uses certain parts of a person’s immune system to fight disease. Immunotherapy for colorectal cancer has been shown to be effective in a small subset of patients with a certain biomarker, MSI, or dMMR.

Immunotherapy is only recommended if you haven’t already had treatment with a checkpoint inhibitor, such as pembrolizumab or nivolumab. All colorectal cancer patients of all stages should know their MSI/MMR status!

  • Pembrolizumab (Keytruda®): is an option for patients who have the MSI-H or d-MMR biomarkers. This treatment is indicated for adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a MSI-H or dMMR biomarker, including patients with solid tumors that have progressed following prior treatment and who have no alternative treatment options.

  • Nivolumab (Opdivo®): is for use in MSI-H or dMMR metastatic colorectal cancer. Nivolumab has been approved for metastatic colorectal cancer patients whose cancer either progressed after being treated with a fluoropyrimidine, oxaliplatin, and irinotecan, or did not respond to those treatments.

  • Ipilimumab (Yervoy®): may be used in combination with nivolumab as a treatment option for metastatic colorectal cancer with MSI-H or dMMR cancer following the progression on a fluoropyrimidine, oxaliplatin, and irinotecan.
  • Dostarlimab (Jemperli ®): Colorectal cancer treatment by stage can be straightforward in the early stages, but it can become incredibly complicated once the cancer progresses. Your Guide in the Fight includes more detailed colorectal cancer treatment by stage for stages III and IV (recurrent) cancers.

Immunotherapies

Immunotherapy uses certain parts of a person’s immune system to fight disease. Immunotherapy for colorectal cancer has been shown to be effective in a small subset of patients with a certain biomarker, MSI, or dMMR.

Immunotherapy is only recommended if you haven’t already had treatment with a checkpoint inhibitor, such as pembrolizumab or nivolumab. All colorectal cancer patients of all stages should know their MSI/MMR status!

  • Pembrolizumab (Keytruda®): is an option for patients who have the MSI-H or d-MMR biomarkers. This treatment is indicated for adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a MSI-H or dMMR biomarker, including patients with solid tumors that have progressed following prior treatment and who have no alternative treatment options.

  • Nivolumab (Opdivo®): is for use in MSI-H or dMMR metastatic colorectal cancer. Nivolumab has been approved for metastatic colorectal cancer patients whose cancer either progressed after being treated with a fluoropyrimidine, oxaliplatin, and irinotecan, or did not respond to those treatments.

  • Ipilimumab (Yervoy®): may be used in combination with nivolumab as a treatment option for metastatic colorectal cancer with MSI-H or dMMR cancer following the progression on a fluoropyrimidine, oxaliplatin, and irinotecan.
  • Dostarlimab (Jemperli ®): Colorectal cancer treatment by stage can be straightforward in the early stages, but it can become incredibly complicated once the cancer progresses. Your Guide in the Fight includes more detailed colorectal cancer treatment by stage for stages III and IV (recurrent) cancers.

Any patient receiving chemotherapy containing 5-FU or capecitabine should undergo DPD testing prior to beginning treatment.

Any patient receiving chemotherapy containing 5-FU or capecitabine should undergo DPD testing prior to beginning treatment.

Champion Stories

So many people look for information and hope when a diagnosis hits. Our Champion Stories Hub
showcases the resilience, strength, and heart of relentless champions of hope.

Sara Alvarenga

Life before CRC was busy as a young 33 year old mom to two young kids. Aside from raising kids and the routine challenges of life, life was relatively carefree. My husband and I both worked full time and made a good living for our family. We were in the process of becoming debt free in the hopes of buying a new home for our children to grow up in.

Our carefree life changed dramatically in December 2018.

Champion Stories

So many people look for information and hope when a diagnosis hits. Our Champion Stories Hub showcases the resilience, strength, and heart of relentless champions of hope.

Sara Alvarenga

Life before CRC was busy as a young 33 year old mom to two young kids. Aside from raising kids and the routine challenges of life, life was relatively carefree. My husband and I both worked full time and made a good living for our family. We were in the process of becoming debt free in the hopes of buying a new home for our children to grow up in.

Our carefree life changed dramatically in December 2018.