Rectal versus left-sided colon cancers: Clinicopathological differences observed in a pooled analysis of 4,182 patients enrolled to 8 clinical trials from the ARCAD database

• Published in: Journal of clinical oncology Vol. 35; no. 4_suppl; p. 675
• Main Authors: Salem, Mohamed E., Yin, Jun, Renfro, Lindsay A., Weinberg, Benjamin Adam, Maughan, Tim, Adams, Richard, Van Cutsem, Eric, Falcone, Alfredo, Tebbutt, Niall C., Seymour, Matthew T., Diaz-Rubio, Eduardo, Aranda, Enrique, Bokemeyer, Carsten, Heinemann, Volker, De Gramont, Aimery, Grothey, Axel, Marshall, John, Sargent, Daniel J.
• Format: Journal Article
• Language: English
• Published: 01.02.2017
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2017.35.4_suppl.675

Abstract only 675 Background: Recent retrospective analysis of CALGB/SWOG 80405 showed that left-sided colon cancers (LCC) respond differently to biological therapy compared with right-sided tumors. However, differences between rectal cancers (RC) and LCC remain undefined. Herein, we report our exploration of differences between these two groups. Methods: Individual patient data from 4182 patients (pts) with metastatic colorectal cancers, enrolled onto 8 first-line randomized trials, were pooled. Only pts with tumor locations that were clearly defined as LCC (splenic flexure to sigmoid) or RC were included in this analysis. Differences in pt characteristics and disease factors according to LCC vs. RC were identified. The prognostic effect of primary tumor location on OS and PFS was quantified via multivariable Cox proportional hazards modeling stratified by treatment arm within each study and adjusting for age, sex, performance status, and prior surgery. Results: In total, 2,479 (59%) pts with LCC and 1,703 (41%) pts with RC were identified. Pts with RC, compared with LCC, were more likely to be male (68% vs. 62%, p < 0.001), have lung metastases (mets) (56% vs. 37%, p < 0.001), and have 2 or more metastatic sites (64% vs. 60%, p < 0.02), whereas pts with LCC were more likely to have liver mets (84% vs. 76%, p < 0.001). RC had a greater frequency of KRAS mutations (41% vs. 37%, p = 0.04) than LCC but there were no differences in the frequency of BRAF mutations (5% vs. 4%, p = 0.2). In multivariable analysis, no differences in OS or PFS were observed between pts with LCC vs. RC. While risk of death did not differ by primary tumor location, across all pts with LCC or RC, those with liver mets had a 17% increased risk of death compared to those with lung mets (HR = 1.17, p = 0.03) after adjusting for effects of other variables. Forthcoming prognostic analysis of LCC vs. RC within grouped backbone treatments (e.g., FOLFOX and FOLFIRI) is underway. Conclusions: Tumors arising in the rectum may carry clinical and molecular features that are distinct from LCC. Further investigations are warranted to determine whether RC should be treated with the same chemo backbone and biological therapy as LCC.