The treatment depends on the staging of the cancer. When colorectal cancer is caught at early stages (with little spread) it can be curable. However, when it is detected at later stages (when distant metastases are present) it is less likely to be curable.
Surgery remains the primary treatment while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors.
Because colon cancer primarily affects the elderly, it can be a challenge to determine how aggressively to treat a particular patient, especially after surgery. Clinical trials suggest that otherwise fit elderly patients fare well if they have adjuvant chemotherapy after surgery, so chronological age alone should not be a contraindication to aggressive management.
Surgeries can be categorised into curative, palliative, bypass, fecal diversion, or open-and-close.
Curative Surgical treatment can be offered if the tumor is localized.
- Very early cancer that develops within a polyp can often be cured by removing the polyp (i.e., polypectomy) at the time of colonoscopy.
- In colon cancer, a more advanced tumor typically requires surgical removal of the section of colon containing the tumor with sufficient margins, and radical en-bloc resection of mesentery and lymph nodes to reduce local recurrence (i.e., colectomy). If possible, the remaining parts of colon are anastomosed together to create a functioning colon. In cases when anastomosis is not possible, a stoma(artificial orifice) is created.
- Curative surgery on rectal cancer includes total mesorectal excision (lower anterior resection) or abdominoperineal excision.
In case of multiple metastases, palliative (non curative) resection of the primary tumor is still offered in order to reduce further morbiditycaused by tumor bleeding, invasion, and its catabolic effect. Surgical removal of isolated liver metastases is, however, common and may be curative in selected patients; improved chemotherapy has increased the number of patients who are offered surgical removal of isolated liver metastases.
If the tumor invaded into adjacent vital structures which makes excision technically difficult, the surgeons may prefer to bypass the tumor (ileotransverse bypass) or to do a proximal fecal diversion through a stoma.
The worst case would be an open-and-close surgery, when surgeons find the tumor unresectable and the small bowel involved; any more procedures would do more harm than good to the patient. This is uncommon with the advent of laparoscopy and better radiological imaging. Most of these cases formerly subjected to open and close procedures are now diagnosed in advance and surgery avoided.
Laparoscopic-assisted colectomy is a minimally-invasive technique that can reduce the size of the incision and may reduce post-operative pain.
As with any surgical procedure, colorectal surgery may result in complications including
- wound infection, Dehiscence (bursting of wound) or hernia
- anastomosis breakdown, leading to abscess or fistula formation, and/or peritonitis
- bleeding with or without hematoma formation
- adhesions resulting in bowel obstruction. A 5-year study of patients who had surgery in 1997 found the risk of hospital readmission to be 15% after panproctocolectomy, 9% after total colectomy, and 11% after ileostomy
- adjacent organ injury; most commonly to the small intestine, ureters, spleen, or bladder
- Cardiorespiratory complications such as myocardial infarction, pneumonia, arrythmia, pulmonary embolism etc
Chemotherapy is used to reduce the likelihood of metastasis developing, shrink tumor size, or slow tumor growth. Chemotherapy is often applied after surgery (adjuvant), before surgery (neo-adjuvant), or as the primary therapy (palliative). The treatments listed here have been shown in clinical trials to improve survival and/or reduce mortality rate and have been approved for use by the US Food and Drug Administration. In colon cancer, chemotherapy after surgery is usually only given if the cancer has spread to the lymph nodes (Stage III). At the 2008 annual meeting of the American Society of Clinical Oncology, researchers announced that colorectal cancer patients that have a mutation in the KRAS gene do not respond to certain therapies, those that inhibit the epidermal growth factor receptor (EGFR)--namely Erbitux (cetuximab) and Vectibix (panitumumab).Following recommendations by ASCO, patients should now be tested for the KRAS gene mutation before being offered these EGFR-inhibiting drugs. In July 2009, the US Food and Drug Administration (FDA) updated the labels of two anti-EGFR monoclonal antibody drugs (panitumumab (Vectibix) and cetuximab (Erbitux)) indicated for treatment of metastatic colorectal cancer to include information about KRAS mutations.
However, having the normal KRAS mutation does not guarantee that these drugs will benefit the patient.
The trouble with the KRAS mutation is that it's downstream of EGFR, says Richard Goldberg, MD, director of oncology at the Lineberger Comprehensive Cancer Center at the University of North Carolina. It doesn't matter if you plug the socket if there's a short downstream of the plug. The mutation turns [EGFR] into a switch that's always on. But this doesn't mean that having normal, or wild-type, KRAS is a fail-safe. It isn't foolproof, cautions Goldberg. If you have wild-type KRAS, you're more likely to respond, but it's not a guarantee. Tumors shrink in response to these drugs in up to 40 percent of patients with wild-type KRAS, and progression-free and overall survival is increased.
The cost benefit of testing patients for the KRAS gene could potentially save about $740 million a year by not providing EGFR-inhibiting drugs to patients who would not benefit from the drugs. With the assumption that patients with mutated Kras (35.6% of all patients) would not receive cetuximab (other studies have found Kras mutation in up to 46% of patients), theoretical drug cost savings would be $753 million; considering the cost of Kras testing, net savings would be $740 million.
- Adjuvant (after surgery) chemotherapy. One regimen involves the combination of infusional 5-fluorouracil, leucovorin, and oxaliplatin(FOLFOX)
- 5-fluorouracil (5-FU) or Capecitabine (Xeloda)
- Leucovorin (LV, Folinic Acid)
- Oxaliplatin (Eloxatin)
- Chemotherapy for metastatic disease. Commonly used first line chemotherapy regimens involve the combination of infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) with bevacizumab or infusional 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) withbevacizumabor the same chemotherapy drug combinations with cetuximab in KRAS wild type tumors
- 5-fluorouracil (5-FU) or Capecitabine
- UFT or Tegafur-uracil
- Leucovorin (LV, Folinic Acid)
- Irinotecan (Camptosar)
- Oxaliplatin (Eloxatin)
- Bevacizumab (Avastin)
- Cetuximab (Erbitux)
- Panitumumab (Vectibix)
- In clinical trials for treated/untreated metastatic disease.
- Bortezomib (Velcade)
- Oblimersen (Genasense, G3139)
- Gefitinib and Erlotinib (Tarceva)
- Topotecan (Hycamtin)
Radiotherapy is not used routinely in colon cancer, as it could lead to radiation enteritis, and it is difficult to target specific portions of the colon. It is more common for radiation to be used in rectal cancer, since the rectum does not move as much as the colon and is thus easier to target. Indications include:
- Colon cancer
- pain relief and palliation - targeted at metastatic tumor deposits if they compress vital structures and/or cause pain
- Rectal cancer
- neoadjuvant - given before surgery in patients with tumors that extend outside the rectum or have spread to regional lymph nodes, in order to decrease the risk of recurrence following surgery or to allow for less invasive surgical approaches (such as a low anterior resection instead of an abdomino-perineal resection)
- adjuvant - where a tumor perforates the rectum or involves regional lymph nodes (AJCC T3 or T4 tumors or Duke's B or C tumors)
- palliative - to decrease the tumor burden in order to relieve or prevent symptoms
Sometimes chemotherapy agents are used to increase the effectiveness of radiation by sensitizing tumor cells if present.
Bacillus Calmette-Guérin (BCG) is being investigated as an adjuvant mixed with autologous tumor cells in immunotherapy for colorectal cancer.
In November 2006, it was announced that a vaccine had been developed and tested with very promising results. The new vaccine, called TroVax, works in a totally different way to existing treatments by harnessing the patient's own immune system to fight the disease. Experts say this suggests that gene therapy vaccines could prove an effective treatment for a whole range of cancers. Oxford BioMedica is a British spin-out from Oxford University specialising in the development of gene-based treatments. Phase III trials are underway for renal cancers and planned for colon cancers.
Treatment of liver metastases
According to the American Cancer Society statistics in 2006, over 20% of patients present with metastatic (stage IV) colorectal cancer at the time of diagnosis, and up to 25% of this group will have isolated liver metastasis that is potentially resectable. Lesions which undergo curative resection have demonstrated 5-year survival outcomes now exceeding 50%.
Resectability of a liver metastasis is determined using preoperative imaging studies (CT or MRI), intraoperative ultrasound, and by direct palpation and visualization during resection. Lesions confined to the right lobe are amenable to en bloc removal with a right hepatectomy (liver resection) surgery. Smaller lesions of the central or left liver lobe may sometimes be resected in anatomic segments, while large lesions of left hepatic lobe are resected by a procedure called hepatic trisegmentectomy. Treatment of lesions by smaller, non-anatomic wedge resections is associated with higher recurrence rates. Some lesions which are not initially amenable to surgical resection may become candidates if they have significant responses to preoperative chemotherapy or immunotherapy regimens. Lesions which are not amenable to surgical resection for cure can be treated with modalities including radio-frequency ablation (RFA), cryoablation, and chemoembolization.
Patients with colon cancer and metastatic disease to the liver may be treated in either a single surgery or in staged surgeries (with the colon tumor traditionally removed first) depending upon the fitness of the patient for prolonged surgery, the difficulty expected with the procedure with either the colon or liver resection, and the comfort of the surgery performing potentially complex hepatic surgery.
A study published in 2009 found that Aspirin reduces risk of colorectal neoplasia in randomized trials and inhibits tumor growth and metastases in animal models. The influence of aspirin on survival after diagnosis of colorectal cancer is unknown. Several reports including a prospective cohort of 1,279 people diagnosed with stages I-III (non-metastatic) colorectal cancer have suggested a significant improvement in cancer-specific survival in a subset of patients using aspirin.
Cancer diagnosis very often results in an enormous change in the patient's psychological wellbeing. Various support resources are available from hospitals and other agencies which provide counseling, social service support, cancer support groups, and other services. These services help to mitigate some of the difficulties of integrating a patient's medical complications into other parts of their life.