Patients with colorectal cancer whose primary tumor is situated on the left side of the colon survive significantly longer than patients whose cancer starts on the right side, says new research to be presented at a meeting next month.
The study – the largest of its kind so far to look at tumor location in colorectal cancer – is a retrospective analysis of data from a large clinical trial designed to compare the effectiveness of two drugs for treating metastatic colorectal cancer.
The analysis shows that patients whose primary tumor is on the left of the colon (the side comprising the descending colon, sigmoid colon, and rectum) have a significantly longer survival than patients whose primary tumor is on the right side (where the cecum and ascending colon are located).
Lead author Alan P. Venook, a professor of medicine at the University of California-San Francisco (UCSF), explains that while previous studies have suggested tumor site can influence clinical outcomes in colorectal cancer, the effect they observed in their analysis is much bigger than they expected.
The study will be presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL, June 3-7, 2016.
ASCO President Julie M. Vose says this unexpected discovery “could answer some long-standing questions about why certain patients do better than others.”
The data came from a clinical trial that compared bevacizumab and cetuximab in combination with chemotherapy as initial therapy for metastatic colorectal cancer.
In their main analysis, the researchers used data on 293 patients with right-sided primary tumors and 732 patients with left-sided primary tumors.
This analysis found that patients with left-sided primary tumors had a median overall survival of 33.3 months, compared with 19.4 months in patients with right-sided primary tumors.
Of the patients treated with cetuximab, those with left-sided primary tumors lived 36 months, while patients with right-sided primary tumors lived 16.7 months.
The analysis showed a similar pattern for patients treated with bevacizumab: 31.4 months overall survival for those with left-sided tumors and 24.2 months for those with right-sided tumors.
Another way to look at these results is from the point of view of tumor location first, then treatment. This shows if the tumor was on the right, patients receiving bevacizumab had a longer survival than patients receiving cetuximab (24.2 months and 16.7 months, respectively).
Conversely, patients with left-sided tumors treated with cetuximab lived 36 months, while those receiving bevacizumab lived 31.4 months.
As the clinical trial comparing the two drugs was under way, it was discovered that mutations in the KRAS gene is an important factor in the use of cetuximab.
When the researchers analyzed the data just for patients with KRAS mutations, they found a similar pattern to the previous results: patients with left-sided tumors lived longer compared with patients with right-sided tumors.
The researchers conclude that whether the primary tumor was on the left or the right likely influenced the effectiveness of the treatments the patients received in the trial.
They are now looking into the molecular biology mechanisms that might explain such differences.
“These findings will likely change the way we approach colorectal cancer treatment and research, even as we seek to more deeply understand the biology driving the difference in outcomes between right- and left-sided cancers.”
Prof. Alan P. Venook
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