Review question
We performed a systematic review to investigate whether people with incurable colorectal cancer, without symptoms, in which the cancer has spread to a different part of the body (metastasised), live longer and maintain quality of life, when you give chemotherapy straight away or wait until disease-related symptoms occur (delayed chemotherapy).
Background
One in five people with colorectal cancer cannot be cured. For them, the best treatment is palliative chemotherapy. Chemotherapy can cause side effects, such as diarrhoea or liver failure. If a person is diagnosed with incurable colorectal cancer, but has not developed symptoms yet, one possible intervention strategy could be to delay chemotherapy until symptom do appear, to avoid side effects and discomfort for the person receiving the treatment.
We wanted to explore whether delaying chemotherapy treatment would have an effect on survival and other relevant outcomes, such as toxicity, and quality of life, compared to initiating chemotherapy straight away.
Study characteristics
We included three randomised clinical trials. In these trials, people with metastatic and incurable colorectal cancer, without symptoms, received chemotherapy straight away (standard group) or their chemotherapy was delayed (intervention group). There were a total of 176 participants In the standard groups and 175 in the intervention groups.
Key results
The available data allowed us to complete analyses for overall survival and toxicities. Participants with metastatic, incurable colorectal cancer without symptoms, who received chemotherapy straight away, did not live longer than those whose chemotherapy was delayed until symptoms appeared. For toxicities measures, our findings were inconclusive due to sparse data from only two trials and few participants. There were insufficient data to compare other outcomes of interest, such as quality of life, progression-free survival (the length of time during and after treatment that a person lives with the disease, but it does not get worse), and compliance with chemotherapy (whether a participant was able to complete the chemotherapy regimen).
Quality of the evidence
Based on very sparse data and uncertainty of the evidence, we were unable to establish whether there was a difference in overall survival and other important outcomes in people with metastatic, incurable, colorectal cancer, who received chemotherapy either straight away or waited until after symptoms had appeared.
Based on a limited number of trials, very sparse data, and uncertainty of the evidence, this review was unable to establish whether there was a difference in overall survival or other clinically relevant outcomes, between immediate or delayed chemotherapy in persons with metastatic, incurable, colorectal cancer. The results should be interpreted with caution.
For patients with asymptomatic, incurable, metastatic colorectal cancer, palliative, systemic treatment can be started immediately, or can be delayed until disease-related symptoms occur. How the potential survival benefit of starting palliative, systemic treatment immediately after diagnosis weighs up against the potential side effects is currently under debate, and was investigated in this review.
To assess the effects of immediate versus delayed chemotherapy, with or without targeted therapy, on overall survival, toxicity, quality of life, progression-free survival, and compliance with chemotherapy for individuals with asymptomatic, metastatic, incurable colorectal cancer.
We searched CENTRAL; 2018, Issue 8, MEDLINE Ovid, Embase Ovid, PsycINFO, the World Health Organization International Clinical Trials Registry Platform, and Clinicaltrials.gov, from inception to 23 August 2018. We did not apply limitations based on language or date of publication. We searched the reference lists of all included studies to identify trials that may not have been identified from the electronic searches.
Randomised controlled trials evaluating immediate versus delayed chemotherapy in persons with asymptomatic, metastatic, incurable colorectal cancer.
We applied standard methodological procedures, according to the recommendations of Cochrane and Cochrane Colorectal Cancer. Two review authors independently reviewed the studies identified by literature searches, selected relevant trials, extracted data, and assessed risk of bias of the included studies. We used the Cochrane tool to assess risk of bias, Review Manager 5 software for meta-analysis, GRADE methods to evaluate the quality of the evidence, and GRADEpro GDT software to develop a 'Summary of findings' table.
We included three randomised controlled trials (351 participants) investigating immediate versus delayed chemotherapy in people diagnosed with asymptomatic, metastatic, incurable colorectal cancer. Giving immediate versus delayed chemotherapy may make little or no difference to overall survival (hazard ratio (HR) 1.17, 95% confidence interval (CI) 0.93 to 1.46; 3 studies, 351 persons; low-quality evidence). For toxicity, giving immediate versus delayed chemotherapy may make little or no difference to the risk of grade 3 or 4 nausea and vomiting (risk ratio (RR) 0.84, 95% CI 0.31 to 2.25; 2 studies, 140 persons; very low-quality evidence), stomatitis (RR 1.10, 95% CI 0.47 to 2.55; 2 studies, 140 persons; very low-quality evidence), or diarrhoea (RR 0.69, 95% CI 0.34 to 1.40; 2 studies, 140 persons, very low-quality evidence). We are uncertain whether delayed chemotherapy made a difference to quality of life (very low-quality evidence), progression-free survival (low-quality evidence), or compliance with chemotherapy (low-quality evidence), as we had insufficient data to pool for these outcomes.