How soon after surgery for colorectal cancer should chemotherapy be started?

The present study evaluated the association between time until initiation of adjuvant chemotherapy and survival in colorectal cancer patients. The main findings were that a shorter time until adjuvant chemotherapy improves survival rates in patients with resected colorectal cancer.

Colorectal cancers that are within the muscle wall of the colon (stage I), have spread to surrounding tissues and local organs (stage II) or have spread to lymph nodes (stage III) are initially treated with surgery. Stages II and III often receive chemotherapy after surgery, or adjuvant chemotherapy. However, the optimal timing from surgery to initiation of adjuvant chemotherapy is unknown.

Most clinical trials state that chemotherapy should be initiated within six to eight weeks after surgery. No trial has tested the effect of extending this time interval on patients’ health and survival. Such trials are not likely to be carried out. This is because delaying treatment may be misinterpreted as withholding treatment from a patient.

This paper looks at results from 10 clinical trials (with a total of 15,410 patients) where the time between surgery and initiation of chemotherapy varied between three to twenty six weeks. Six of these ten studies treated patients with a standard Fluorouracil-based chemotherapy; data was not available for the other four. Analysis focused on the impact of the time interval to starting chemotherapy on two main outcomes: overall survival (OS) and disease free survival (DFS). OS is defined as the percentage of patients who have survived for a defined period of time. DFS is the percentage of patients without signs and symptoms of cancer during this time.

Findings: A 4-week delay in the time to initiation of adjuvant chemotherapy was associated with a significant decrease (14%) in both OS and DFS. Based on these results the authors calculated that a delay to 8 weeks and 12 weeks would reduce 5-year survival (OS after 5 years) to 54% and 48%, respectively.

This report therefore provides evidence that it is best to start adjuvant chemotherapy as soon as possible following surgery.

However, results were limited by the lack of information about patients’ characteristics, preoperative therapy, and the chemotherapeutic regimens used in the selected trials.