Better Survival for Colon Cancer Patients with Left-Sided Tumors

Location Matters, Says Study to Be Presented at Major Cancer Meeting

By Elizabeth Fernandez

stock illustration of a transparent female body with colon highlightedThe chances of surviving colon cancer could depend on which side of the colon the cancer strikes.

A national study led by a UC San Francisco oncologist has found that patients with metastatic colon cancer that develops on the left side of the colon survive significantly longer than those with cancer that develops on the right side. Additionally, the researchers learned that a standard drug used to treat colon cancer offers little benefit for patients whose cancer originated on the right side.

The findings from the large, federally-funded clinical trial suggest that colon cancer is actually not one but a number of different diseases. Until more is known, the researchers say that colon cancer originating on the right side should be treated differently than colon cancer occurring on the left side.

The research will be released on May 18, 2016, at 5 p.m. (ET), ahead of the 2016 annual meeting of the American Society of Clinical Oncology (ASCO).

Could Change How Colon Cancer is Treated

“All colon cancer is not created equally,” said UCSF oncologist Alan P. Venook, MD, principal investigator of the study. He is the Madden Family Distinguished Professor of Medical Oncology and Translational Research and the Shorenstein Associate Director for Program Development at the UCSF Helen Diller Family Comprehensive Cancer Center.

Portrait of Alan P. Venook
Alan P. Venook, MD

“It is very clear that the biology of the colon on the right side is different from the biology on the left side,” Venook said. “Previous research suggested that tumor location could affect clinical outcomes, but the effects we observed in this trial appeared to be far great than we expected. This could potentially change the way that colon cancer is treated.”

This year’s ASCO meeting June 3-7 in Chicago is expected to draw 30,000 oncology professionals from around the world to discuss key advances and groundbreaking research in cancer. The theme of the meeting is Collective Wisdom: The Future of Patient-Centered Care and Research.

More than 5,200 scientific abstracts were accepted for the meeting. The colon cancer abstract is one of five chosen for special advance presentation. Venook will formally present the colon cancer trial results on June 5.

“This is the largest study to date of tumor location in colorectal cancer, and it strongly suggests that this unexpected factor could answer some long-standing questions about why certain patients do better than others,” said ASCO President Julie M. Vose, MD, MBA. “It is also an important reminder, in this exciting era of precision medicine, that genomics is not the only source of insight into how cancers should be studied and treated.”

'Should Not be Surprising' Cancers are Different Biologically

The study was launched in 2004 and involved 293 patients with right-sided primary tumors and 732 patients with left-sided primary tumors.

Earlier research within the same study, the Phase III CALGB/SWOG 80405 clinical trial, established a new benchmark in 2014 in the treatment of patients with metastatic colorectal cancer and set a new expectation for how long patients could live with the particularly lethal disease. In that phase of the trial, median survival was approximately 29 months, with about 10 percent of the patients living more than five years, a very encouraging length compared to two decades ago.

Human colon cancer cells with the cell nuclei stained red and the protein E-cadherin stained green.
Human colon cancer cells with the cell nuclei stained red and the protein E-cadherin stained green. Image by the NCI Center for Cancer Research

In the new analysis, the median age of patients in the trial was 61 for those with right-sided tumors (the cecum and ascending colon); for patients with left-sided cancer, (the descending colon, sigmoid colon, and rectum) the media age was 57. Men comprised more than half of the patients.

Those with cancer on the left side survived overall for 33.3 months, while people with tumors on the right side survived for 19.4 months. Left-sided cancer patients treated with cetuximab added to first-line chemotherapy lived on average 36 months, while those with right-sided cancer on the drug lived for 16.7 months.

“This is a really big difference,” said Venook. “We historically believed that left-sided cancer presents itself earlier due to symptoms, and that patients with right-sided cancer are likelier to have a greater tumor burden before developing symptoms. But the right and left sides of the colon arise from different tissue in the embryo, so it should not be surprising that they are different biologically.

“To be clear,” he continued, “the side of the primary is undoubtedly a surrogate marker for biological characteristics of the cancers. Until that underlying biology is understood, right-sided colon cancer should be considered different than left-sided colon cancer.”    

Co-authors include Donna Niedzwiecki, PhD, of Duke University; Federico Innocenti, MD, PhD, of the University of North Carolina at Chapel Hill; Richard Goldberg, MD, of the Ohio State University Comprehensive Cancer Center; and Heinz-Josef Lenz, MD, FACP, of the Keck School of Medicine of the University of Southern California.  

“We thank our patients,” Venook said. “We are indebted to them for their willingness to participate in clinical trials and to provide tissue and blood samples to enable researchers to study the molecular details of cancers. These are selfless contributions to science and to future patients. We’re also grateful for the courage of one of our medical fellows, Dr. Rachel Pearline, who died last year of gastric cancer. Rachel was responsible for some of the data acquisition and analysis of this study. She had an extraordinary commitment to patient care and she was deeply committed to this study.” 

The study was supported by the National Institutes of Health U10CA180821, U10CA180882. The study also received funding and support from BMS, Genentech and Imclone in collaboration with the National Cancer Institute.

UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospitals in San Francisco and Oakland – and other partner and affiliated hospitals and healthcare providers throughout the Bay Area.