Colon Cancer

Such patients have disease spread at the time of diagnosis, usually into the surrounding tissues, lymph nodes, liver and lungs. Virtually any organ in the body can be involved and extensive metastases may be already present at the time of diagnosis.
The liver is the organ commonly involved at the time of metastases.
In such patients, a curative or a radical surgery is not possible. These patients can achieve disease control with appropriate therapy but cannot be cured. The treatment intent is palliative with the aim being to improve and then maintain a good quality of life, relieve/avoid pain, halt disease spread & obtain control of the cancer. Surgery is only advocated if palliation is required, as in relieving intestinal obstruction due to the cancer, or to control bleeding from an ulcerated tumour. Other than this there is usually no indication for surgery.
All biopsy samples of the cancer must be sent for further molecular profiling and next generation sequencing. Mismatch Repair Deficiency and Microsatellite Status must be tested as well.
A dMMR status diagnosed by MSI-H ( microsatellite high) status opens up the option of using Immunotherapy upfront rather than chemotherapy. Such patients are usually younger and may have a Hereditary Colon Cancer Syndrome. They respond extremely well to Immunotherapy and can achieve excellent tumour control with prolonged disease survival.
In case of a proficient MMR status (MSS- microsatellite stable), Immunotherapy has limited benefit. Such patients must undergo detailed molecular testing to look for targetable mutations like HER2, NTRK and mutations that may reduce benefit from targeted therapy- like RAS, RAF. The entire panel of mutations must be tested. The results guide the therapy chosen.
Chemotherapy is required in MSS patients where immunotherapy is not an option. Regimens used are FOLFOX, CAPEOX, FOLFIRI & FOLFOXIRI. The protocol chosen depends on the patient profile like age, general condition, co-morbidities, previously treated or newly diagnosed. Usually a patient will be sequentially treated with all available drugs as the cancer relapses after periods of control.
RAS & RAF mutations usually reduce benefit from targeted therapies like Cetuximab & Panitumumab. In these patients a targeted agent like Bevacizumab is added to the chemotherapy protocol. This drug blocks the blood supply of the cancer and potentiates the effect of the chemotherapy.
Absence of RAS/RAF mutations allows the addition of Cetuximab or Panitumumab to the chemotherapy. Bevacizumab is also an option for these patients with chemotherapy.
HER2 or NTRK mutations require the addition of targeted agents directed towards these mutations.
Chemotherapy plus targeted therapy or Immunotherapy is recommended for disease control till there is disease control or development of toxicity. Discontinuing chemotherapy following cancer control and continuing only targeted therapy as maintenance is also a valid option.
Participation of young patients in promising clinical trials of new agents is recommended as available treatment options are exhausted.