The two-week wait means patients should see a specialist for their first appointment within two weeks of seeing a GP with suspected cancer symptoms.
But new research has found a higher number of deaths in cancer patients whose GPs do not regularly use the pathway.
Published in the British Medical Journal (BMJ), the study, which was funded by Cancer Research UK and National Institute for Health Research, examined data from 215,284 English cancer patients in 2009.
Death rates increased by 7% for patients whose GP practices used the two-week wait least often compared with practices with a typical referral rate.
Meanwhile, patients from the best performing practices had a 4% lower death rate compared to those with a typical rate.
The data was gathered from 8,049 general practices in England where patients were diagnosed or first treated in 2009 and followed up to 2013.
Lead author Professor Henrik Moller, an epidemiologist at King’s College London, said 2,400 excess deaths occurred in the worst performing practices but this figure was likely to be conservative.
He added: “Increasing a GP’s cancer awareness and their likelihood of urgently referring cancer patients could help reduce deaths.
“There’s a fine line to tread between using the urgent referral route regularly and using it too much - which the NHS isn’t equipped to respond to.
“But if GP practices which use the two-week route rarely were to use it more often, this could reduce deaths of cancer patients.”
Sara Hiom, Cancer Research UK’s director of early diagnosis, said. “This crucial evidence shows that the earlier a cancer patient is diagnosed the better the chances of survival. “Earlier cancer can be treated more effectively with a wider range of treatment options.
“And tumours can progress if there’s a delay in time to diagnosis and starting treatment.
“It’s never been clearer that reducing late diagnosis saves lives and this research adds to our understanding of what can be done about it.”
Dr Rosie Loftus, joint chief medical officer of Macmillan Cancer Support, said: “GPs encounter cancer comparatively rarely, but will see large numbers of patients with a variety of symptoms which may or may not be to do with cancer, making diagnosis more difficult.
“It is therefore critical that GPs have tools available to help them spot cancer at the earliest possible stage.”