Starting Chemotherapy Before Surgery Improves Outcomes in Locally Advanced Colon Cancer
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Colon and rectal cancers, cancers of the large bowel, are the 3rd most common cancer worldwide. Approximately 40% are diagnosed at a locally advanced stage, also described as stage 2 and 3 colorectal cancer. Immediate surgery is established for earlier, stage 1 colon cancer, but in locally advanced disease the question remains: "Should we operate immediately, or begin with tumor-shrinking chemotherapy and then perform surgery?" Results from an important clinical trial addressing this question were published on January 19, 2023 in Journal of Clinical Oncology (JCO) .
In stage 2, cancer has reached the colon's outer layer (serosa) or surrounding tissue (mesocolon) without spreading to lymph nodes (T3-T4a N0).
In stage 3, cancer has spread beyond the colon into surrounding tissue and nearby lymph nodes (T1-T4a N1-N2).
Differences Between Colon and Rectal Cancer
Because locally advanced rectal cancer has different biology, beginning treatment with neoadjuvant (preoperative) chemotherapy or radiotherapy has become more widely accepted. Rectal anatomy differs from the colon, and neighboring organs and preservation of anal function are important. Studies suggest better outcomes with surgery after neoadjuvant chemotherapy for locally advanced colon cancer, leading some physicians to favor this approach. However, there is no consensus, and uncertainty remains about which patients are suitable.
Potential advantages include:
- early systemic treatment to reduce micrometastatic risk,
- shrinking the primary tumor to facilitate surgical removal, and
- better adherence when systemic treatment is given before surgery.
Micrometastasis refers to tiny deposits of cancer cells, approximately 0.2 mm or smaller, settling separately in other organs or tissues as cells spread from the primary tumor. These cells may develop into a new tumor. Detecting micrometastases early is difficult. Early chemotherapy may eliminate or control them and reduce recurrence risk.
The FOxTROT Study
FOxTROT (Fluoropyrimidine Oxaliplatin and Targeted Receptor Pre-Operative Therapy) was a randomized controlled study of neoadjuvant chemotherapy in colon cancer. It involved 1053 patients with locally advanced disease (T3-4 N0-2), evaluating preoperative and postoperative chemotherapy.
One group received preoperative oxaliplatin and fluoropyrimidine chemotherapy, while the other received chemotherapy only after surgery. Some patients were also randomly assigned to receive or not receive panitumumab.
A total of 525 patients had immediate surgery followed by adjuvant chemotherapy; 528 received 6 weeks of neoadjuvant chemotherapy, surgery and adjuvant chemotherapy.
FOxTROT demonstrated benefits from preoperative chemotherapy in locally advanced colon cancer.
Recurrent or residual disease rates at 2 years were:
- 17% in the neoadjuvant group, versus
- 22% in the adjuvant group.
Patients receiving preoperative chemotherapy also had fewer serious postoperative complications.
Panitumumab did not increase neoadjuvant chemotherapy's benefit. However, tumors with dMMR (deficient mismatch repair) derived very little benefit from neoadjuvant treatment.
In summary, neoadjuvant chemotherapy in locally advanced colon cancer:
- Reduced residual or recurrent disease,
- Facilitated tumor removal and increased complete (R0) surgical resection,
- Improved adherence compared with postoperative adjuvant chemotherapy.
FOxTROT suggests that preoperative chemotherapy may be an effective option for locally advanced colon cancer, although further research is needed.
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Further Information: Colon and Rectal Cancer Staging
The AJCC/UICC 8th staging system is the latest method for cancer staging.
It determines stage through factors including tumor size (T), lymph node involvement (N) and metastases (M). Each factor has a hierarchy of substages. Combining them establishes the overall cancer stage .
The AJCC/UICC 8th staging system was developed to improve staging and treatment planning. Alongside stage, it helps determine prognosis and treatment options.
Final colon cancer stages under TNM can be classified as follows:
- Stage 0: Cancer is confined to the inner lining, or mucosa, of the colon (Tis).
- Stage I: Cancer extends from the inner lining to the outer layer (serosa), without lymph node involvement (T1-T2 N0).
- Stage II: Cancer extends into surrounding tissue (mesocolon), without lymph node involvement (T3-T4a N0).
- Stage III: Cancer has spread to nearby lymph nodes (T1-T4a N1-N2).
- Stage IV: Cancer has spread to organs or tissues outside the colon (T1-T4a N0-N2 M1).
Colorectal Cancer Survival by Stage
SEER (Surveillance, Epidemiology, and End Results) is a US database tracking cancer epidemiology and survival. Its 5-year relative survival estimates for colorectal cancer vary by stage.
The relative 5-year survival rate is the percentage surviving at least 5 years after diagnosis. According to SEER, the overall 5-year relative survival rate for colorectal cancer, all stages combined, is approximately 65%.
The source gives the following SEER 5-year relative survival rates by stage:
- Stage 0: 92.4%
- Stage I: 87.4%
- Stage II: 67.3%
- Stage III: 53.4%
- Stage IV: 14.9%
Relative survival compares survival over a specified period in people with a disease with expected survival based on factors such as age, sex and ethnicity.
These rates should be used only as reference estimates because relative survival varies with many factors. Recent advances and newly approved treatments may also not yet be reflected in the statistics.
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