The Impact of Mismatch Repair Status in Colorectal Cancer on the Decision to Treat With Adjuvant Chemotherapy: An Australian Population‐Based Multicenter Study

• Published in: The oncologist (Dayton, Ohio) Ohio), 2016-05, Vol.21 (5), p.618-625
• Main Authors: He, Emily Y., Hawkins, Nicholas J., Mak, Gabriel, Roncolato, Felicia, Goldstein, David, Liauw, Winston, Clingan, Philip, Chin, Melvin, Ward, Robyn L.
• Format: Article
• Language: English
• Subjects: Adjuvant chemotherapy; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Chemotherapy, Adjuvant; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; DNA Mismatch Repair; Female; Fluorouracil - therapeutic use; Gastrointestinal Cancer; Humans; Leucovorin - therapeutic use; Male; Microsatellite Instability; Middle Aged; Mismatch repair deficiency; Neoplasm Staging; Organoplatinum Compounds - therapeutic use; Regression Analysis; Treatment decisions
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2015-0530

Background. Testing for mismatch repair (MMR) status in colorectal cancer (CRC) may provide useful prognostic and predictive information. We evaluated the impact of such testing on real‐world practice regarding adjuvant chemotherapy for patients with resected CRC. Patients and Methods. A total of 175 patients with stage II and III mismatch repair‐deficient (MMRD) CRC were identified from an Australian population‐based study of incident CRCs. Their treatment decisions were compared with those for a cohort of 773 stage‐matched patients with mismatch repair‐proficient (MMRP) CRCs. The effect of MMR status, age, and pathologic characteristics on treatment decisions was determined using multiple regression analysis. Results. Overall, 32% of patients in stage II and 71% of patients in stage III received adjuvant chemotherapy. Among the stage II patients, those with MMRD cancer were less likely to receive chemotherapy than were MMRP cases (15% vs. 38%; p < .0001). In this group, the treatment decision was influenced by age, tumor location, and T stage. MMR status influenced the treatment decision such that its impact diminished with increasing patient age. Among patients with stage III tumors, no difference was found in the chemotherapy rates between the MMRD and MMRP cases. In this group, age was the only significant predictor of the treatment decision. Conclusion. The findings of this study suggest that knowledge of the MMR status of sporadic CRC influences treatment decisions for stage II patients, in an era when clear recommendations as to how these findings should influence practice are lacking. Implications for Practice: Microsatellite instability (MSI) is a molecular marker of defective DNA mismatch repair found in 15% of sporadic colorectal cancers. Until recently, expert guidelines on the role of MSI as a valid biomarker in the selection of stage II patients for adjuvant chemotherapy were lacking. Conducted at a time when the clinical utility of routine MSI testing was unclear, this study found that clinicians were influenced by MSI status in selecting stage II patients for chemotherapy. Furthermore, the impact of MSI on treatment decisions was greatest in younger patients and declined progressively until age 80 years, when no effect was found. 摘要 背景. 对结直肠癌 (CRC) 进行错配修复 (MMR) 状态检验可能提供有用的预后和预测信息。我们评价了这种检验在真实世界临床实践中对手术切除后 CRC 患者辅助化疗的影响。 患者与方法. 我们从澳大利亚基于人群的偶发性 CRC 研究中, 共鉴别出 175 例有错配修复缺陷 (MMRD) 的 II 期和 III 期 CRC 患者。将他们的治疗决策与 773 例分期匹配的错配修复功能完善的 CRC 患者队列进行比较。