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Right-sided colorectal tumors have worse outcomes
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Patients with stage III and high-risk stage II colorectal cancer had worse DFS if they had right-sided tumors compared with left-sided tumors, according to results of a study scheduled for presentation at the Gastrointestinal Cancers Symposium.
“This is the first study to show that unselected patients with right-sided tumors had a worse DFS compared [with] left-sided tumors,” Mark P. Saunders, MD, PhD, MBBS, MRCP, FRCR, consultant clinical oncologist at The Christie NHS Foundation Trust in Manchester, United Kingdom, and colleagues wrote. “This implies that prognosis is influenced primarily by greater recurrence rather than the contributing factors that influence OS.”
Registry studies and meta-analyses have shown that patients with right-sided colorectal tumors who develop metastatic disease have a worse prognosis than patients with left-sided tumors. Those with left-sided tumors also may have greater benefit from treatment with epidermal growth factor receptor inhibitors. The PETACC8 study recently confirmed these findings, but only after patients had relapsed.
Results from the SCOT study showed 3 months of oxaliplatin-containing adjuvant chemotherapy was noninferior to 6 months among patients with stage III and high-risk stage II colorectal cancer. The study comprised 6,088 patients from 244 cancer centers from six countries, who were randomly assigned between March 27, 2008, and Nov. 29, 2013.
Saunders and colleagues sought to determine whether tumor sidedness had an impact on DFS in the SCOT study. Researchers divided the evaluable study population of 3,219 patients (median age, 65 years) based on whether they had right-sided (n = 1,207; 53% men; 41% tumor size 4; 17% stage II) or left-sided (n = 2,012; 66% men; 24% T4; 21% stage II) tumors.
Significantly fewer patients with right-sided tumors achieved 3-year DFS (73% vs. 80%; HR = 1.4; 95% CI 1.21-1.61).
Adjusting for T- and N-stage reduced the HR to 1.21 (95% CI, 1.05-1.4).
The data did not suggest that sidedness affected the impact of 3 months vs. 6 months of chemotherapy on 3-year DFS (right-sided, HR = 1.04; 95% CI, 0.84-1.29; left-sided, HR = 0.91; 95% CI, 0.75-1.09).
Researchers noted the cohort size limited further subset analysis. – by Chuck Gormley
Disclosures: Cancer Research UK and Medical Research Council funded this study. Saunders reports honoraria and consultant/advisory roles with Amgen, Merck, Roche and Servier. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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David H. Ilson, MD, PhD
Investigators from the SCOT trial compared 3 months vs. 6 months of adjuvant chemotherapy with a fluorinated pyrimidine and oxaliplatin in stage III colon cancer. In over 6,000 patients treated, 3 months of adjuvant chemotherapy was not inferior to 6 months of therapy. This result was robust for lower-risk T3 or N1 patients receiving 3 months of capecitabine and oxaliplatin. Although noninferiority could not be demonstrated for 3 months of therapy compared with 6 months of therapy for higher-risk T4 or N2 disease, the small absolute survival difference led these investigators to consider 3 months of capecitabine and oxaliplatin as a care standard irrespective of risk status.
These results are practice-changing. The IDEA pooled analysis of 3 months vs. 6 months of adjuvant chemotherapy in 10,000 patients, including those treated on the SCOT trial, shows remarkable consistency across trials and endorses the use of 3 months of adjuvant capecitabine and oxaliplatin in low-risk stage III colon cancer.
It is now recognized that tumors arising in the right side of the colon have inferior OS in stage III and stage IV disease compared with left-sided tumors, and also have resistance to EGFR inhibitors and higher rates of RAS mutation and microsatellite instability-high status. The SCOT investigators now report for the first time that 3-year DFS is significantly inferior for right- vs. left-sided tumors, even with adjuvant therapy (73% vs 80%). When researchers corrected this analysis for imbalances in stage, 3-year DFS remained inferior for right-sided tumors.
Importantly, despite the worse prognosis, extending adjuvant chemotherapy out to 6 months in right-sided tumors did not improve 3-year DFS compared with 3 months of therapy. These data emphasize the need to stratify trials in stage III disease by right- and left-sided primary tumors, and that novel treatment strategies for right-sided stage III cancers need to be developed.
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